Clinical Studies

Abstracts are presented below for clinical studies on Neem.

  • Botanical Name: Azadirachta Indica

  • Ayurvedic Name: Nimba

  • Common Name: Neem

Azadirachta Indica

Plant Phytonutrient Profile

1: J Ethnopharmacol. 2007 Jan 21; [Epub ahead of print]

Antibacterial, antisecretory and antihemorrhagic activity of Azadirachta indica
used to treat cholera and diarrhea in India.

Thakurta P, Bhowmik P, Mukherjee S, Hajra TK, Patra A, Bag PK.

Department of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road,
Kolkata 700019, India.

Indigenous uses of Azadirachta indica A. juss (Maliaceae) (locally known as
neem) leaves in different parts of India for curing gastrointestinal disorder
such as diarrhea and cholera is wide spread. The objective of the present study
was to evaluate the antibacterial and antisecretory activity of neem extract
against Vibrio cholerae, a causative agent of watery diarrhea such as cholera.
The methanol extract of neem leaf was tested for its antibacterial,
antisecretory and antihemorrhagic activity against Vibrio cholerae. Azadirachta
indica extract had significant antibacterial activity against the
multi-drug-resistant Vibrio cholerae of serotypes O1, O139 and non-O1, non-O139.
The minimum inhibitory concentration reached by 50% (MIC(50)) and 90% (MIC(90)),
and minimum bactericidal concentration for the extract were 2.5, >5, and
10mg/ml, respectively. Neem extract showed antisecretory activity on Vibrio
cholerae induced fluid secretion in mouse intestine with inhibition values of
27.7%, 41.1%, 43.3%, 57.0%, and 77.9% at doses of 100, 200, 300, 450 and
1800mg/kg, respectively. Oral administration of the extract inhibited hemorrhage
induced by Vibrio cholerae in mouse intestine at a dose >/=300mg/kg. The results
obtained in this study give some scientific support to the uses of neem employed
by the indigenous people in India employed for the treatment of diarrhea and
dreadful disease cholera.

PMID: 17314018 [PubMed - as supplied by publisher]

2: J Agric Food Chem. 2007 Feb 21;55(4):1389-1393. Epub 2007 Jan 31.

Influence of Physicochemical Parameters of Neem (Azadirachta indica A Juss) Oils
on Nitrification Inhibition in Soil.

Kumar R, Devakumar C, Sharma V, Kakkar G, Kumar D, Panneerselvam P.

Divisions of Agricultural Chemicals and Agronomy, Indian Agricultural Research
Institute, New Delhi 110 012, India.

The technology for the production of neem oil coated urea (NOCU) developed by
the Indian Agricultural Research Institute is in the pipeline for adaption by
several Indian fertilizer industries. Use of nitrification inhibitors is one of
the methods of improving the nitrogen use efficiency (NUE) of nitrogenous
fertilizers in agriculture. However, standard specifications for the neem oil as
a raw material of NOCU are desired. Accordingly, the present study was
undertaken to evaluate 25 samples of neem oils comprising 11 samples of expeller
grade (EG) oils, 8 samples of cold-pressed (CP) oils, 3 samples of
solvent-extracted oils, and 2 commercial formulations. NOCU was prepared using
these oils (5000 ppm of urea-N). The soils fertilized with NOCUs (200 ppm of
urea-N) were incubated at 27 degrees C and 50% water-holding capacity for a
period of 15 days. Nitrapyrin (0.5% of N) coated urea served as the reference
and prilled urea as control. Samples were analyzed for NH4+-N, NO2--N, and
NO3--N using standard methods. The percent nitrification inhibition (NI) was
calculated, and the results revealed that all of the neem oils caused NI ranging
from 4.0 to 30.9%. Two samples of EG oils and two commercial formulations were
found to be the best, causing 27.0-30.9% NI. Iodine, acid, and saponification
values and meliacin content of all of the oils were analyzed and correlated with
NI. The results revealed the direct influence of meliacin content of the neem
oils on NI, which, however, was found to be negatively correlated with
saponification and iodine values. There is, therefore, a need to introduce new
Bureau of Indian Standards (BIS) specifications for neem oils as raw materials
of NOCU. Keywords: Neem (Azadirachta indica); neem oils; nitrification
inhibition; meliacins; NOCU; iodine value; saponification value; acid value.

PMID: 17263551 [PubMed - as supplied by publisher]

3: J Egypt Public Health Assoc. 1998;73(5-6):649-65.

Response and effect of two plant crude extracts on mosquito larvae Culex

El-Ela NA, Talha M, El-Aziz AA.

Tropical Health Dept., High Institute of Public Health, Alexandria University.

The response and effect of two plant crude extract from dry Damsissa (Ambrosia
maritima) and Neem seeds (Azadirachta indica) were tested against the first and
third instar larvae of mosquito (Culex pipiens). The results showed that both
extracts had a larvicidal effect. Neem seed extract was more toxic than Damsissa
extract against both the first and third instar larvae. In addition, the young
larvae (first instar) were more susceptible to Neem seeds than the old ones
(third instar) as revealed from the LC50 values, while Damsissa showed nearly
the same effect against both stages. Meanwhile, treatment of Neem seed extracts
resulted in prolongation of the larval period accompanied with a decrease in
larval activity. Moreover, the effect of the two extracts on larval total
esterase isozymes was examined. Neem extract showed an adverse effect on the
third instar larvae, since only one band (E1) was observed and the other 4 bands
disappeared at all concentrations used, as compared with untreated control
larvae (El, E2, E3, E4, and E5). Meanwhile, Damsissa extract treatment of the
third instar larvae showed an additional band located between E3 and E4, and the
absence of two bands (E2 and E3) after treatment with 0.5x10(4), 1x10(4) and
1.5x10(4) ppm, while treatment with 0.25x10(4) ppm did not result in any changes
in larval total esterase.

PMID: 17217029 [PubMed - indexed for MEDLINE]

4: J Econ Entomol. 2006 Dec;99(6):2010-4.

Bioactivity of neem, Azadirachta indica, against spittlebug Mahanarva
fimbriolata (Hemiptera: Cercopidae) on sugarcane.

Garcia JF, Grisoto E, Vendramim JD, Botelho PS.

Departamento de Entomologia, Fitopatologia e Zoologia Agricola-ESALQ/USP-Caixa
Postal: 09, CEP: 13418-900, Piracicaba-Sao Paulo, Brazil. [email protected]

The effect of neem, Azadirachta indica A. Juss, on some biological parameters of
Mahanarva fimbriolata (Stil) (Hemiptera: Cercopidae) was studied in the
laboratory by using NeemAzal-T/S, Nimkol-LS, and an aqueous neem seed extract.
Initially, the LC,, was estimated for nymphs. Later, nymphs fed on sugarcane,
Saccharum officinarum L., roots were sprayed with the respective LC,, for each
product. The adults were maintained in cages on sugarcane plants sprayed at the
base with the maximum rate recommended commercially for the crop (3 liter/ha).
Moistened cotton discs surrounding the base of the plant were used as
oviposition substrates. The LCso values estimated for NeemAzal, Nimkol, and
aqueous extract were 0.014, 0.225, and 0.611%, respectively. There was a
reduction in spittlebug longevity, regardless of sex, in relation to the
control. Males exposed to the neem products, and aqueous extract showed
longevity reductions of approximately 50%, whereas for females the reductions
were 55-60%. The neem products and extract reduced fecundity by 75-85%.
Morphological and physiological changes were observed in 9% of the eggs from
individuals submitted to NeemAzal. Neem-based products, especially NeemAzal,
have potential for the control of M. fimbriolata.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17195667 [PubMed - in process]

5: Indian J Physiol Pharmacol. 2006 Jul-Sep;50(3):241-9.

Effect of aqueous extract of neem (Azadirachta indica) leaves on offensive and
diffensive gastric mucosal factors in rats.

Dorababu M, Joshi MC, Bhawani G, Kumar MM, Chaturvedi A, Goel RK.

Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu
University, Varanasi 221 005.

Standardized aqueous extract of Neem (Azadirachta indica) leaves (AIE) has been
reported to show both ulcer protective and ulcer healing effects in normal as
well as in diabetic rats. To study the mechanism of its ulcer protective/healing
actions, effects of AIE (500 mg/ kg) was studied on various parameters of
offensive acid-pepsin secretion in 4 hr pylorus ligation, pentagastrin (PENTA, 5
microg/kg/hr)-stimulated acid secretion and gastric mucosal proton pump activity
and defensive mucin secretion including life span of gastric mucosal cells in
rats. AIE was found to inhibit acid-pepsin secretion in 4 hr pylorus ligated
rats. Continuous infusion of PENTA significantly increased the acid secretion
after 30 to 180 min or in the total 3 hr acid secretion in rat stomach perfusate
while, AIE pretreatment significantly decreased them. AIE inhibited the rat
gastric mucosal proton pump activity and the effect was comparable with that of
omeprazole (OMZ). Further, AIE did not show any effect on mucin secretion though
it enhanced life span of mucosal cells as evidenced by a decrease in cell
shedding in the gastric juice. Thus, our present data suggest that the ulcer
protective activity of AIE may be due to its anti-secretary and proton pump
inhibitory activity rather than on defensive mucin secretion. Further, acute as
well as sub acute toxicity studies have indicated no mortality with 2.5 g/kg
dose of AIE in mice and no significant alterations in body or tissues weight,
food and water intake, haematological profile and various liver and kidney
function tests in rats when treated for 28 days with 1 g/kg dose of AIE.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 17193895 [PubMed - indexed for MEDLINE]

6: Tree Physiol. 2006 Dec;26(12):1565-78.

Patchy stomatal behavior in broad-leaved trees grown in different habitats.

Takanashi S, Kosugi Y, Matsuo N, Tani M, Ohte N.

Laboratory of Forest Hydrology, Division of Environmental Science and
Technology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502,
Japan. [email protected]

Effects of heterogeneity in stomatal behavior on gas-exchange characteristics of
leaves from four tree species growing in different climates, including
temperate, tropical monsoon and tropical rain forest, were investigated by
combining gas-exchange measurements and the pressure-infiltration method. Field
observations indicated linear relationships between whole-leaf conductance and
the ratio of infiltrated to non-infiltrated leaf area (open stomata area) in
Dipterocarpus sublamellatus Foxw. and Neobalanocarpus heimii (King) Ashton in a
tropical rain forest in Peninsular Malaysia, whereas the ratio of infiltrated to
non-infiltrated area rapidly increased up to the whole-leaf conductance at which
the entire leaf was infiltrated in Cinnamomum camphora Sieb. in a temperate
evergreen forest in Japan and in Azadirachta indica Juss. in a tropical monsoon
area in Thailand. These results strongly suggest small ranges in bell-shaped
stomatal conductance distributions in C. camphora and A. indica and bimodal
stomatal conductance distributions in D. sublamellatus and N. heimii. The values
of normalized maximum carboxylation rate at 25 degrees C (V(cmax25)) derived
from gas-exchange measurements were not constant, but decreased with decreasing
whole-leaf conductance in D. sublamellatus and N. heimii. A gas-exchange model
analysis revealed a linear relationship between whole-leaf conductance and the
ratio of infiltrated to non-infiltrated leaf area for bimodal stomatal
conductance distributions, whereas for bell-shaped distributions, the
relationships were nonlinear. Midday depression of apparent V(cmax25) in these
species was mainly caused by bimodal stomatal closure. The bimodal stomatal
distribution model could also explain diurnal changes in photosynthetic
assimilation and transpiration rates in these species.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17169896 [PubMed - in process]

7: Turkiye Parazitol Derg. 2005;29(1):3-6.

In vitro assessment of anti - cutaneous leishmaniasis activity of some Sudanese

Fatima F, Khalid A, Nazar N, Abdalla M, Mohomed H, Toum AM, Magzoub M, Ali MS.

Institute of Nuclear Medicine, Molecular Biology and Oncology,University of
Gezera, Sudan.

Examination of crude methanol extracts of four Sudanese plants (Azadirachta
indica, Acacia nilotica, Balanites aegyptiaca and Allium sativa) revealed that
only three species had a considerable in-vitro anti-leishmanial activity on
Leishmania major promastigotes. The plants Azadrachta indica, Allium sativa, and
Acacia nilotica gave a LC50 of 10.2, 4.94, and 89.38 microg/ml, respectively.
Extracts of Balanites aegyptiaca had a moderate biological activity on L major

PMID: 17167733 [PubMed - as supplied by publisher]

8: Phytother Res. 2006 Dec 13; [Epub ahead of print]

Antiproliferative effect on human cancer cell lines after treatment with
nimbolide extracted from an edible part of the neem tree (Azadirachta indica).

Roy MK, Kobori M, Takenaka M, Nakahara K, Shinmoto H, Isobe S, Tsushida T.

National Food Research Institute, 2-1-12, Kannondai, Tsukuba, Ibaraki 305-8642,

Nimbolide, a triterpenoid extracted from the flowers of the neem tree
(Azadirachta indica), was found to have antiproliferative activity against some
cancer cell lines. Treatment of cells with 0.5-5.0 mum concentrations of
nimbolide resulted in moderate to very strong growth inhibition in U937, HL-60,
THP1 and B16 cell lines. Flow cytometric analysis of U937 cells showed that
nimbolide treatment (1-2.5 mum) resulted in cell cycle disruption by decreasing
the number of cells in G0/G1 phase, with initial increases in S and G2/M phases.
Cells exposed to a higher dose of nimbolide for a longer period displayed a
severely damaged DNA profile, resulting in a remarkable increase in the number
of cells in the sub-G1 fraction, with a reciprocal decrease of cells in all
phases. Quantification of the expression of phosphatidylserine in the outer cell
membrane showed that doses of nimbolide higher than 0.4 mum exerted remarkable
lethality, with over 60% of cells exhibiting apoptotic features after exposure
to 1.2 mum nimbolide. The antiproliferative effect of nimbolide and its
apoptosis-inducing property raise hope for its use in anticancer therapy by
enhancing the effectiveness of cell cycle disruption. Copyright (c) 2006 John
Wiley & Sons, Ltd.

PMID: 17163581 [PubMed - as supplied by publisher]

9: Vet Parasitol. 2007 Mar 31;144(3-4):328-37. Epub 2006 Dec 8.

Impact of the botanical insecticide Neem Azal((R)) on survival and reproduction
of the biting louse Damalinia limbata on angora goats.

Habluetzel A, Carnevali F, Lucantoni L, Grana L, Attili AR, Archilei F, Antonini
M, Valbonesi A, Abbadessa V, Esposito F, van der Esch SA.

Department of Experimental Medicine and Public Health, Via M. Scalzino 3,
University of Camerino, 62032 Camerino (MC), Italy.

Secondary metabolites present in the neem tree (Azadirachta indica A. Juss,
Meliaceae), exhibit a wide range of biological activities in insects. However,
few studies have been undertaken to assess the potential of neem products as
insecticides for the control of ectoparasites of domestic animals. This study
was undertaken to estimate the efficacy of Neem Azal((R)), an azadirachtin-rich
extract of neem seeds, in controlling Damalinia limbata (Phthiraptera) louse
infestation of angora goats. The study was conducted on a fibre animal farm
situated in Central Italy. Groups of 11-12 goats were treated with Neem
Azal((R)) at an azadirachtin concentration of 650ppm or 125ppm, with
Neguvon((R)) or were left untreated. Their louse burden was assessed fortnightly
to monthly for 22 weeks. A reduction in louse densities of 76-96% was observed
from week 2 to week 18 after treatment with the neem solution containing
azadirachtin at a concentration of 650ppm. At the lower test concentration
(125ppm) a reduction of 60-92% could be recorded from week 2 to week 14. Neem
Azal((R)) was found to reduce the survival of both adult and nymph stages of D.
limbata and to interfere with oviposition and oogenesis of female lice. A
decrease in oviposition was observed in neem exposed female lice and the
examination of their ovaries revealed morphological alterations in both
vitellogenic and previtellogenic ovarioles at the follicular and germinal level.
Since neem compounds target different life stages and physiological processes of
D. limbata, the development of insecticide resistance by biting lice exposed to
neem-based insecticides appears unlikely. For this reason and for its prolonged
activity, which in principle allows angora goats to be protected for a large
part of the mohair production cycle, neem-based insecticides may have a
potential interest for mohair producing breeders.

PMID: 17161539 [PubMed - in process]

10: Nat Prod Res. 2006 Oct;20(12):1036-40.

A new tetracyclic triterpenoid from the leaves of Azadirachta indica.

Siddiqui BS, Afshan F, Sham-Sul-Arfeen, Gulzar T.

H.E.J. Research Institute of Chemistry, International Centre for Chemical
Sciences, University of Karachi, Karachi-75270, Pakistan.
[email protected]

A new tetracyclic triterpenoid zeeshanol
[25,26,27-trinor-apotirucalla-(apoeupha)-6alpha-, 21-dihydroxy, 7alpha-acetoxy,
1,14,22-tri-en-3, 16-dione] (1) along with a known constituent
desfurano-6alpha-hydroxyazadiradione (2) have been isolated from the methanolic
extract of the leaves of Azadirachta indica. The structure and the relative
configurations of 1 were determined by the spectroscopic method (1H- and
13C-NMR, IR, and MS) and 2D-NMR experiments.

PMID: 17127654 [PubMed - in process]

11: Chemosphere. 2007 Feb;67(1):80-8. Epub 2006 Nov 17.

The toxic effects of neem extract and azadirachtin on the brown planthopper,
Nilaparvata lugens (Stal) (BPH) (Homoptera: Delphacidae).

Senthil Nathan S, Choi MY, Paik CH, Seo HY, Kim JD, Kang SM.

Plant Environment Division, Honam Agricultural Research Institute (HARI),
National Institute of Crop Science (NICS), Rural Development Administration
(RDA), #381 Songhak-dong, Iksan, Chonbuk, 570-080, Republic of Korea.
[email protected]

Extracts of neem (Azadirachta indica A. Juss) are used in the developing world
for many purposes including management of agricultural insect pests. The effects
of different neem extracts (aqueous (NSKEaq), ethanol (NSKEeth) and hexane
(NSKEhex)) on mortality, survival and weight of the brown planthopper,
Nilaparvata lugens (Stal) (BPH) (Homoptera: Delphacidae) third and fourth
nymphal instars were investigated. When fed rice plants treated with neem
derivatives in bioassays, the survival of BPH nymphs is affected. Comparisons
were made with the pure neem limonoid, azadirachtin (AZA) to ascertain its role
as a compound responsible for these effects. AZA was most potent in all
experiments and produced almost 100% nymphal mortality at 0.5 ppm and higher
concentrations. When higher concentrations were applied, the effects appeared
shortly after treatment and mortality was higher. Many insects died after
remaining inactive for several days or during prolonged moulting. At lower
concentrations, if moulting was achieved, disturbed growth and abnormalities
were then likely to occur in the moulting process. Nymphs that were chronically
exposed to neem extract showed a reduction in weight (45-60%). The results
clearly indicate the simple NSKE (aqueous, ethanolic or both), containing low
concentrations of AZA, can be used effectively to inhibit the growth and
survival of BPH.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17113126 [PubMed - in process]

12: J Biotechnol. 2007 Feb 1;128(2):281-9. Epub 2006 Oct 21.

Enhanced production of azadirachtin by hairy root cultures of Azadirachta indica
A. Juss by elicitation and media optimization.

Satdive RK, Fulzele DP, Eapen S.

Plant Biotechnology and Secondary Products Section, Nuclear Agriculture and
Biotechnology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085,

Azadirachtin is one of the most potent biopesticides so far developed from a
plant sources. Influence of different culture media and elicitation on growth
and production of azadirachtin by hairy root cultures of Azadirachta indica was
studied. Out of the three media tested, namely Ohyama and Nitsch, Gamborg's and
Murashige and Skoog's basal media, hairy roots cultured on Ohyama and Nitsch's
basal medium produced maximum yield of azadirachtin (0.0166% dry weight, DW).
Addition of biotic elicitor enhanced the production of azadirachtin by
approximately 5-fold (0.074% DW), while signal compounds such as jasmonic acid
and salicylic acid showed a approximately 6 (0.095% DW) and approximately 9-fold
(0.14% DW) enhancement, respectively, in the production of azadirachtin as
compared to control cultures on Ohyama and Nitsch medium. Extracts from hairy
roots were found to be superior to those from the leaves for antifeedant
activity against the larvae of Spodoptera litura.

PMID: 17109981 [PubMed - in process]

13: Pak J Pharm Sci. 2006 Oct;19(4):322-5.

Clinical investigation of hypoglycemic effect of seeds of Azadirachta-inidca in
type-2 (NIDDM) diabetes mellitus.

Waheed A, Miana GA, Ahmad SI.

Department of Pharmacology & Therapeutics, Army Medical College, Rawalpindi.

The present study was designed to investigate clinically the hypoglycemic effect
of seeds of Azadirachta indica in Type-2 diabetes mellitus. After assaying
fasting plasma and urinary glucose, 10 patients of type-2 diabetes mellitus with
no previous medication, 10 patients of type-2 diabetes mellitus taking oral
hypoglycemic agents with history of inadequate control and six control subjects
were given low (0.5 g tid) and high (2 g tid) doses of powdered part, aqueous
extract and alcoholic extract of Azadirachta indica for 14 days. On 15th day
blood and urine samples for glucose were taken. Based on results obtained it was
found that Azadirachta indica has significant hypoglycemic activity in high dose
and can be successfully combined with oral hypoglycemic agents in type-2
diabetic patients whose diabetes is not controlled by these agents.

PMID: 17105712 [PubMed - indexed for MEDLINE]

14: Tissue Cell. 2006 Dec;38(6):361-71. Epub 2006 Nov 13.

Effects of a neem extract on blood feeding, oviposition and oocyte
ultrastructure in Anopheles stephensi Liston (Diptera: Culicidae).

Lucantoni L, Giusti F, Cristofaro M, Pasqualini L, Esposito F, Lupetti P,
Habluetzel A.

Department of Experimental Medicine and Public Health, University of Camerino,
Camerino, Italy.

Secondary metabolites of the neem tree (Azadirachta indica A. Juss., Meliaceae)
exhibit a wide range of biological activities in insects. However, few studies
have addressed the effects of neem extracts or compounds in arthropods of
medical importance. In this study, a laboratory strain of Anopheles stephensi
was used to assess the effects of a commercial formulation (Neem Azal) (NA)),
containing azadirachtin A at 34%, on blood feeding, oviposition and oocyte
ultrastructure. Oral administration of Neem Azal) to A. stephensi females
through artificial blood meals did impair blood intake and oviposition in a
concentration dependent manner. Similar results were obtained on females, which
had consumed Neem Azal) in sucrose solution before taking a blood meal of plain
blood. Neem treated females displayed a delay in oocyte development in both the
phase of vitellogenesis and the phase of choriogenesis. The ultrastructural
studies on ovaries from Neem Azal) treated females revealed distinct structural
modifications indicative of: (i) a complete block of oogenesis, (ii) impairment
of vitellogenesis and vitelline envelope formation, (iii) a severe degeneration
of follicle cells. In agreement with results obtained in other insects, this
study indicates that Neem Azal) impairs hormone control of oogenesis and exerts
a cytotoxic effect on both follicular cells and oocytes of the Asian malaria
vector A. stephensi.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17097701 [PubMed - indexed for MEDLINE]

15: Neotrop Entomol. 2006 Jul-Aug;35(4):500-5.

[Toxicity of neem (Azadirachta indica A. Juss) formulations for twospotted
spider mite and Euseius alatus de leon and Phytoseiulus macropilis (Banks)
(Acari: Phytoseiidae)]

[Article in Portuguese]

Brito HM, Gondim MG Jr, de Oliveira JV, da Camara CA.

Depto. Agronomia, Univ. Federal Rural de Pernambuco, Rua Dom Manoel de Medeiros
s/n, Recife, PE.

The toxicity of selected commercial formulations of neem on Tetranychus urticae
Koch (Acari: Tetranychidae) and two predatory mites Euseius alatus De Leon and
Phytoseiulus macropilis (Banks) was studied. Topical toxicity was tested with
the commercial formulations (Natuneem, Neemseto and Callneem) and extract of
neem's seeds at concentration 1%, compared to the standard acaricide abamectin
at concentration of 0.3 ml/L and the control treatment (distilled water). Based
on the best performance against T. urticae through topical contact, the
formulation Neemseto was selected to be evaluated using different concentrations
against eggs, and residual and repellent effects on adults of the mites. Egg
treatment consisted of dipping eggs into Neemseto dilutions and control
treatment for five seconds. In addition, residual and repellent effects of
Neemseto for adult mites consisted of using leaf discs dipped into the dilutions
for five seconds. The toxicity of Neemseto on eggs and adults was greater for T.
urticae compared to the toxicity observed for the predatory mites. Neemseto was
repellent for T. urticae and E. alatus when tested at the concentrations of
0.25, 0.50 and 1.0%, and did not affect P. macropilis. Neemseto using all
concentrations, while for the predatory mites significant reduction of mite
fecundity was only observed at the largest concentrations reduced the fecundity
of T. urticae significantly. So Neemseto, among tested neem formulations,
performed better against the twospotted spider mite and exhibited relatively low
impact against the predatory mites studied.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't

PMID: 17061799 [PubMed - indexed for MEDLINE]

16: Asian Pac J Cancer Prev. 2006 Jul-Sep;7(3):467-71.

Antioxidative and modifying effects of a tropical plant Azadirachta indica
(Neem) on azoxymethane-induced preneoplastic lesions in the rat colon.

Arakaki J, Suzui M, Morioka T, Kinjo T, Kaneshiro T, Inamine M, Sunagawa N,
Nishimaki T, Yoshimi N.

Tumor Pathology, University of the Ryukyus Faculty of Medicine, Okinawa
903-0215, Japan. [email protected]

The purpose of the present study was to examine whether Neem leaf (Azadirachta
indica) has short-term chemopreventive effects on endpoint preneoplastic lesions
involved in rat colon carcinogenesis and might also exert antioxidative
activity. Forty- two male F344 rats were randomly divided into 6 experimental
groups. Groups 1 to 4 were given a subcutaneous injection of azoxymethane (AOM,
20 mg/kg body weight) once a week for 2 weeks. Starting one week before the
first injection of AOM, rats in groups 2 to 4 received an aqueous extract of
Neem leaf (20, 100, and 250 mg/kg, respectively) by gavage 3 times per week, for
5 weeks. Rats in group 5 also were given the Neem extract by gavage feeding 3
times per week for 5 weeks, while group 6 served as untreated controls. The
experiment was terminated 5 weeks after the start. Dietary feeding of the Neem
extract at all dose levels significantly inhibited the induction of aberrant
crypt foci (ACF) (P<0.0002), when compared to the AOM-treated group (group 1).
In groups 2 to 4, treatment of rats with the Neem extract also significantly
decreased the proliferating cell nuclear antigen (PCNA) labeling indices
(P<0.0006) of colon epithelium and ACF. Moreover, the Neem extract also showed
antioxidative activity. The finding that dietary Neem has possible
chemopreventive effects in the present short-term colon carcinogenesis bioassay
suggests that longer-term exposure may cause suppression of tumor development.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17059347 [PubMed - indexed for MEDLINE]

17: Trop Biomed. 2006 Jun;23(1):23-30.

Daily feeding of fresh Neem leaves (Azadirachta indica) for worm control in

Chandrawathani P, Chang KW, Nurulaini R, Waller PJ, Adnan M, Zaini CM, Jamnah O,
Khadijah S, Vincent N.

Veterinary Research Institute, 59, Jalan Sultan Azlan Shah, 31400, Ipoh, Perak.

This study was conducted to evaluate the anthelmintic effect of Neem
(Azadirachta indica) on nematode parasites of sheep. Twelve Santa Ines cross
bred sheep from a government farm were randomly selected and equally divided
into control (n = 6) and treated groups (n =6). Faecal egg counts (FEC) using
the modified McMaster technique and the FAMACHA score for assessing clinical
anaemia were carried out daily and recorded for 6 weeks. At the end of the study
all the animals were slaughtered and the total worm count (TWC) was done. The
results of FEC showed that there was no significant difference between the
control and treated group (p = 0.081). However, worm burden estimations showed
that the number of parasites was significantly higher in the control group
compared to the treated group (p < 0.05). This result indicated that feeding
Neem had an effect on worm numbers in sheep, but was not reflected in their
faecal egg counts. Further work is needed to reconfirm the effect of Neem on
helminth infections of sheep.

PMID: 17041548 [PubMed - in process]

18: Int J Oncol. 2006 Nov;29(5):1269-78.

Chemopreventative strategies targeting the MGMT repair protein: augmented
expression in human lymphocytes and tumor cells by ethanolic and aqueous
extracts of several Indian medicinal plants.

Niture SK, Rao US, Srivenugopal KS.

Center for Cancer Biology, Department of Pharmaceutical Sciences, Texas Tech
University Health Sciences Center, Amarillo, TX 79106, USA.

O6-alkylguanines are potent mutagenic, pro-carcinogenic and cytotoxic lesions
induced by exogenous and endogenous alkylating agents. A facilitated elimination
of these lesions by increasing the activity of O6-methylguanine-DNA
methyltransferase (MGMT) is likely to be a beneficial chemoprevention strategy,
which, however, has not been examined. Because, a marginal enhancement of this
protein may be adequate for genomic protection, we studied alterations in MGMT
activity and expression in human peripheral blood lymphocytes and cancer cell
lines induced by water-soluble and alcohol-soluble constituents of several
plants with established antioxidant and medicinal properties. Both the ethanolic
and aqueous extracts from neem (Azadirachta indica), holy basil (Ocimum
sanctum), winter cherry (Withania somnifera), and oregano (Origanum majorana)
increased the levels of MGMT protein and its demethylation activity in a
time-dependent manner with a maximum of 3-fold increase after 72-h treatment.
The extracts from gooseberry (Emblica officinalis), common basil (Ocimum
basilicum), and spearmint (Mentha viridis) were relatively less efficient in
raising MGMT levels. Increased levels of MGMT mRNA accounted at least, in part,
for the increased activity of the DNA repair protein. The herbal treatments also
increased glutathione S-transferase-pi (GSTP1) expression, albeit to a lesser
extent than MGMT. These data provide the first evidence for the upregulation of
human MGMT by plant constituents and raise the possibility of rational dietary
approaches for attenuating alkylation-induced carcinogenesis. Further, they
reveal the putative antioxidant responsiveness of the MGMT gene in human cells.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

PMID: 17016661 [PubMed - indexed for MEDLINE]

19: Immunobiology. 2006;211(9):721-31. Epub 2006 Jun 8.

Neem (Azadirachta indica) leaf preparation induces prophylactic growth
inhibition of murine Ehrlich carcinoma in Swiss and C57BL/6 mice by activation
of NK cells and NK-T cells.

Haque E, Baral R.

Department of Immunoregulation and Immunodiagnostics, Chittaranjan National
Cancer Institute, 37 S P Mookherjee Road, Kolkata 700026, West Bengal, India.

We have reported earlier that pretreatment of mice with neem leaf preparation
(NLP) causes prophylactic growth inhibition of murine Ehrlich's carcinoma (EC)
and B16 melanoma. Using adoptive cell transfer technology, here we have
established that NLP-mediated activation of immune cells may be involved in
tumor growth restriction. Mononuclear cells from blood and spleen of
NLP-activated Swiss and C57BL/6 mice causes enhanced cytotoxicity to murine EC
cells in vitro. Fractionation of spleen cells exhibited greater percentage of
tumor cell lysis in macrophage and B-cell-depleted NK and T-cell-rich fractions.
Flow cytometric analysis revealed in both blood and spleen, NK cells (DX5+ or
NK1.1+) and NK-T cells (CD3+/DX5+ or CD3+/NK1.1+) were increased in number in
Swiss, C57BL/6 and athymic nude mice after pretreatment with NLP. NLP-stimulated
spleen cells showed greater secretion of TNFalpha and IFNgamma. Thus,
NLP-activated NK and NK-T cells in mice may regulate tumor cell cytotoxicity by
enhancing the secretion of different cytotoxic cytokines.

PMID: 17015147 [PubMed - indexed for MEDLINE]

20: Clin Biochem. 2006 Nov;39(11):1080-7. Epub 2006 Aug 5.

Expression of PCNA, cytokeratin, Bcl-2 and p53 during chemoprevention of hamster
buccal pouch carcinogenesis by ethanolic neem (Azadirachta indica) leaf extract.

Subapriya R, Kumaraguruparan R, Nagini S.

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai
University, Annamalainagar-608 002, Tamil Nadu, India.

OBJECTIVES: To evaluate the effect of ethanolic neem leaf extract (ENLE) on cell
proliferation, differentiation and apoptosis associated proteins during
7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP)
carcinogenesis. DESIGN AND METHODS: Hamsters were divided into four groups. The
right buccal pouches of animals in group 1 were painted with 0.5% DMBA three
times a week. Animals in group 2 painted with DMBA as in group 1, received in
addition, intragastric administration of ENLE (200 mg/kg bw) on days alternate
to DMBA application. Group 3 animals were given ENLE (200 mg/kg bw) alone.
Animals in group 4 served as control. All the animals were sacrificed after an
experimental period of 14 weeks. The expression of proliferating cell nuclear
antigen (PCNA), cytokeratin, Bcl-2 and p53 in the buccal pouch tissues were
investigated using immunohistochemical staining. In addition, the expression of
p53 was confirmed by Western blot analysis. RESULTS: Topical application of DMBA
for 14 weeks induced buccal pouch carcinomas associated with increased
expression of PCNA, mutant p53 and Bcl-2 and decreased expression of
cytokeratin. Administration of ENLE significantly inhibited the development of
HBP carcinomas as revealed by decreased expression of PCNA, mutant p53 and Bcl-2
and overexpression of cytokeratin. CONCLUSION: These findings suggest that ENLE
exerts its anticancer properties by inhibiting cell proliferation and inducing
differentiation and apoptosis.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16989797 [PubMed - indexed for MEDLINE]

21: Int J Biol Macromol. 2007 Feb 28;40(3):232-6. Epub 2006 Aug 1.

Identification and partial characterization of a highly active and stable
phospholipase D from Brassica juncea seeds.

Khatoon H, Talat S, Younus H.

Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002,

Phospholipase D (PLD) activity has been identified in some new plant sources
i.e. Brassica juncea (mustard) seeds, Zingibar officinale (ginger) rhizomes and
Azadirachta indica (neem) leaves with the aim of identifying PLDs that possess
high catalytic activity and stability. PLD from mustard seeds (PLD(ms))
exhibited the highest PLD specific activity, which was highly pH and temperature
tolerant. PLD(ms) unlike many plant PLDs exhibited high thermal stability. The
activity of PLD(ms) is optimum in the millimolar concentration of calcium ions
and is independent of phosphatidylinositol-4,5-bisphosphate (PIP(2)). An active
and stable enzyme like PLD(ms) may be utilized in the lipid industry.

PMID: 16949665 [PubMed - in process]

22: Phytomedicine. 2006 Sep;13(8):576-83. Epub 2005 Jun 24.

Native Kenyan plants as possible alternatives to methyl bromide in soil

Rugutt JK, Ngigi AN, Rugutt KJ, Ndalut PK.

Department of Chemistry, Massachusetts College of Liberal Arts, 375 Church
Street, North Adams, MA 0147, USA. [email protected]

Methyl bromide (CH3Br) is a biocidal fumigant used widely in crop production and
commodity preservation worldwide. CH3Br escapes to the stratosphere and releases
bromine atom (Br), which contributes to significant destruction of the ozone
(O3). It is therefore necessary to explore alternatives to CH3Br that are
environmentally safe and suitable for resource-poor African farmers. We present
here the results of a study on the inhibitory activity of crude extracts from
Kenyan medicinal plants against three soil pathogens, Fusarium oxysporum,
Alternaria passiflorae, and Aspergillus niger. Crude organic extracts of
Warburgia ugandensis Sprague, Azadirachta indica A. Juss, Tagetes minuta and
Urtica massaica were active against all soil pathogens, while those from U.
massaica were not. Chromatographic purification of the crude extract of W.
ugandensis provided two pure compounds, muzigadial (1) and muzigadiolide (5).
The minimum inhibitory concentration (MIC value) for muzigadial (1) ranged from
5 to 100mug/ml. Muzigadiolide (5) was not active. Greenhouse tests of W.
ugandensis extracts against F. oxysporium pathogen showed the most effective
inhibitory concentration to be at least 5 mg/ml. Quantitative structure-activity
relationship (QSAR) models were used to rationalize the variation in biological
activities of muzigadial (1), warburganal (2), polygodial (3), ugandensidial
(4), muzigadiolide (5), azadirachtin (6), and CH3Br. The models were based on
several molecular descriptors including LogP, van der Waals surface area
(VDW(A)), van der Waals volume (VDW(v)), dipole moment, total energy,
polarizability, and differences between the highest occupied molecular orbital
and the lowest unoccupied molecular orbital (HOMO-LUMO gap).

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16920513 [PubMed - indexed for MEDLINE]

23: Phytother Res. 2006 Oct;20(10):889-95.

Preventive effects of Azadirachta indica on benzo(a)pyrene-DNA adduct formation
in murine forestomach and hepatic tissues.

Gangar SC, Sandhir R, Rai DV, Koul A.

Department of Biophysics, Basic Medical Sciences Block, Panjab University,
Chandigarh 160014, India.

In the present investigation, the effects of aqueous Azadirachta indica leaf
extract (AAILE) on (3)H-benzo(a)pyrene-DNA [(3)H-B(a)P-DNA] adduct formation,
the status of biotransformation enzymes and reduced glutathione (GSH) content
were evaluated in the forestomach and liver of Balb/c mice. Two weeks of AAILE
treatment reduced the (3)H-B(a)P-DNA adduct levels by 31.6% in forestomach
tissue. Similarly, (3)H-B(a)P-DNA adduct levels were decreased by 34.7% in the
liver of AAILE treated mice compared with their control counterparts. After
AAILE treatment, the cytochrome P450 content decreased, whereas the GSH content
increased significantly in the hepatic tissue. In the forestomach as well as in
the liver, the cytochrome b5 content declined, whereas an increase in
glutathione-S-transferase (GST) activity was observed in both tissues. These
observations suggested that AAILE may have reduced the metabolic activation of
(3)H-B(a)P with enhanced detoxification of its active metabolites, hence the
observed decrease in the levels of (3)H-B(a)P-DNA adducts. These molecular and
biochemical modulations observed at the initiation phase of carcinogenesis seems
to be significant and could be correlated with the chemopreventive effects of A.
indica against B(a)P induced forestomach tumorigenesis. Copyright 2006 John
Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16909440 [PubMed - indexed for MEDLINE]

24: Microbiol Res. 2006 Jul 25; [Epub ahead of print]

Neem (Azadirachta indica a. Juss) components: Candidates for the control of
Crinipellis perniciosa and Phytophthora ssp.

de Rezende Ramos A, Ludke Falcao L, Salviano Barbosa G, Helena Marcellino L,
Silvano Gander E.

Universidade Federal do Para, Centro de Ciencias Biologicas, Depto. Genetica,
Rua Augusto Correa 1, Guama, 66075-110 Belem-PA, Brazil.

Witches' broom and pod rot are the two most devastating diseases of cocoa in
South America and Africa, respectively. Their control by means of
phytosanitation and chemical fungicides is labor-intensive, costly and, in many
cases, environmentally undesirable. Therefore efforts are made in order to
identify alternative, environmentally safe and cost-efficient methods for the
control of these pathogens. Promising candidates are components of the neem tree
(Azadirachta indica), that have been used for centuries in Asia as insecticides,
fungicides, anticonceptionals in popular medicine. Here we report about tests on
the effect of various concentrations of extracts from neem leaves on growth of
mycelia of Crinipellis and Phytophthora and on germination of spores of
Crinipellis. We show a 35% growth reduction of mycelia of Phytophthora on neem
leaf extract media, whereas growth of mycelia of Crinipellis was not affected,
even at the highest concentration of neem leaf extracts used (35%). However, the
most dramatic effect of neem leaf extracts is observed on Crinipellis spore
germination, here the extracts (20-35%) reduced germination almost completely.
Based on these results, we believe that the neem tree might be a source for the
production, on small and medium scale, of an effective and cheap formulation for
the control of Crinipellis and Phytophthora.

PMID: 16872817 [PubMed - as supplied by publisher]

25: Planta Med. 2006 Aug;72(10):917-23. Epub 2006 Jul 20.

Inhibition of colon cancer (HT-29) cell proliferation by a triterpenoid isolated
from Azadirachta indica is accompanied by cell cycle arrest and up-regulation of

Roy MK, Kobori M, Takenaka M, Nakahara K, Shinmoto H, Tsushida T.

National Food Research Institute, Kannondai, Ibaraki, Tsukuba, Japan.
[email protected]

Nimbolide, a natural triterpenoid present in the edible parts of the neem tree (
Azadirachta indica), was found to be growth-inhibitory in human colon carcinoma
HT-29 cells. Nimbolide treatment of cells at 2.5 - 10 microM resulted in
moderate to very strong growth inhibition. Flow cytometric analysis of HT-29
cells showed that nimbolide treatment (2.5 microM, 12 h) caused a 6.5-fold
increase in the number of cells (55.6 %) in the G2/M phase compared with the
control cells (8.8 %). At 48 h, the cell population in the G2/M phase decreased
to 18 %, while that in the G0/G1 phase increased to 52.3 %. Western blot
analysis revealed that nimbolide-mediated G2/M arrest was accompanied by the
up-regulation of p21, cyclin D2, Chk2; and down-regulation of cyclin A, cyclin
E, Cdk2, Rad17. At G0/G1 cell cycle arrest, modulation in the expression of the
cell cycle regulatory molecules was also observed. We found that
nimbolide-induced growth inhibition and cell cycle arrest were not associated
with cellular differentiation. Quantification of cells with respect to the
expression of phosphatidylserine in the outer cell membrane showed an increase
in apoptotic cells by about 13 % after 48 h of nimbolide treatment.

PMID: 16858664 [PubMed - indexed for MEDLINE]

26: J Environ Biol. 2006 Jan;27(1):103-5.

Effective method for extraction of larvicidal component from leaves of
Azadirachta indica and Artemisia annua Linn.

Tonk S, Bartarya R, Maharaj Kumari K, Bhatnagar VP, Srivastava SS.

Department of Chemistry, Faculty of Science, Dayalbagh Educational Institute,
Dayalbagh, Agra-282 005, India.

Leaves of Artemisia annua linn. and Azadirachta indica were extracted in
petroleum ether and hexane respectively by different methods of extraction i.e.
cold extraction, reflux extraction and soxhlet extraction. The crude extract
obtained was tested against third instar larvae of Anopheles stephensi. On
comparison of larval mortality of crude extract obtained by these three methods,
both soxhlet and reflux extraction method showed 100% mortality at 200 ppm after
48 hr in case of A. annua. However LC50 (20 ppm) value of crude extract obtained
by soxhlet extraction showed better results than reflux extraction (35 ppm)
method after 72 hr. In case of A. indica, crude obtained by soxhlet showed 100%
mortality (after 48 hr) at 250 ppm and LC50 of 69 ppm at 72 hr. Reflux
extraction does not show any appreciable mortality even at 250 ppm

Publication Types:
Evaluation Studies
Research Support, Non-U.S. Gov't

PMID: 16850885 [PubMed - indexed for MEDLINE]

27: Phytother Res. 2006 Sep;20(9):814-8.

Pretreatment with neem (Azadirachta indica) leaf preparation in Swiss mice
diminishes leukopenia and enhances the antitumor activity of cyclophosphamide.

Ghosh D, Bose A, Haque E, Baral R.

Department of Immunoregulation and Immunodiagnostics, Chittaranjan National
Cancer Institute, Kolkata-700026, India.

Cancer chemotherapy is associated with several life threatening complications,
including bone marrow suppression and leucopenia. To overcome this problem,
colony stimulating factor (CSF), granulocyte colony stimulating factor (GCSF)
and granulocyte macrophage colony stimulating factor (GMCSF), can be used,
however, these therapeutics are expensive and have several disadvantages,
including tumor growth promoting activities. This study attempted to use an
immunostimulatory neem (Azadirachta indica) leaf preparation (NLP) to prevent
the cyclophosphamide (CYP) induced reduction in the WBC count. Pretreatment of
mice with NLP reduced the extent of leucopenia and neutropenia in normal and
tumor bearing CYP treated mice. NLP pretreatment enhanced in vitro tumor cell
cytotoxicity by peripheral blood mononuclear cells (PBMC) from CYP treated mice
in either normal or tumor bearing conditions. Similarly, NLP pretreatment of
mice enhanced the CYP mediated in vivo tumor growth inhibition and survivability
of the host. Based on these observations, it is concluded that NLP would be an
effective tool to reduce CYP-induced hematological complications. Copyright (c)
2006 John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16807877 [PubMed - indexed for MEDLINE]

28: Bioorg Med Chem Lett. 2006 Aug 15;16(16):4391-4. Epub 2006 Jun 21.

Synthesis and biological activity of amide derivatives of nimbolide.

Sastry BS, Suresh Babu K, Hari Babu T, Chandrasekhar S, Srinivas PV, Saxena AK,
Madhusudana Rao J.

Natural Products Laboratory, Division of Organic Chemistry-I, Indian Institute
of Chemical Technology, Hyderabad.

Nimbolide (1), a limonoid isolated from Azadirachta indica, is the chief
cytotoxic principle in Neem leaves extract. Using nimbolide as a lead compound
for anti-cancer analogue design, a series of nimbolide derivatives have been
synthesized and evaluated for in vitro cytotoxic activity against a panel of
human cancer cell lines. Out of 10 compounds screened 2g, 2h and 2i showed
potent activity.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16793266 [PubMed - indexed for MEDLINE]

29: Eur J Med Chem. 2006 Aug;41(8):997-1002. Epub 2006 Jun 19.

Synthesis and cytotoxicity of novel isomeric C-seco limonoids.

Genupur A, Jesu JL, Srinivasan N, Kamalakaran AS, Sundar RS.

Asthagiri Herbal Research Foundation, 7/1 Thirumazhisai Street, Sundaram Colony,
East Tambaram, Chennai 600059, Tamil Nadu, India.

Attempts to cleave the C-ring in the bioactive limonoids characteristic of the
species Azadirachta indica A. Juss using BF(3) x OEt(2) and (C(4)H(9))(4)NBr
resulted in novel isomeric C-seco limonoids. Structure related cytotoxic
properties of the isomers and the native compounds have been studied using brine
shrimp lethality bioassay (BSLB) method and molecular descriptors viz.,
theoretical and chromatographic hydrophobicity constants, oxidation state and
molecular modelling studies. The O-O diad distances reveal the significance of
the orientation of the furan ring in enhancing the cytotoxicity of the molecule.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16782238 [PubMed - indexed for MEDLINE]

30: J Ethnopharmacol. 2006 Nov 3;108(1):152-4. Epub 2006 Apr 29.

An inventory of the ethnobotanicals used as anthelmintics in the southern Punjab

Jabbar A, Raza MA, Iqbal Z, Khan MN.

Ethnoveterinary Research and Development Centre, Department of Veterinary
Parasitology, University of Agriculture, Faisalabad-38040, Pakistan.
[email protected]

A survey was conducted in southern Punjab, Pakistan, in order to document
existing ethnobotanical knowledge by the herdsmen/key respondents about
anthelmintics in ruminants. A 3-satge process was used to document the plants
being used to treat and/or control helminthes. This paper describes 29 plants to
treat helminthosis in ruminants. The main plants used were Lamium amplexicaule
L., Mallotus philippinensis Muell., Withania somnifera (L.) Dunal., Azadirachta
indica A. Juss., and Citrullus colocynthis (L.) Schrad. A few of these plants
have been scientifically validated for their claim by herdsmen on modern lines
while majority of them still needs investigations. This documentation could
provide a foundation for the scientific study and verification of those plants
which merit such study.

PMID: 16730420 [PubMed - in process]

31: J Ethnopharmacol. 2006 Nov 3;108(1):85-9. Epub 2006 Apr 27.

In vitro screening of six anthelmintic plant products against larval Haemonchus
contortus with a modified methyl-thiazolyl-tetrazolium reduction assay.

Hordegen P, Cabaret J, Hertzberg H, Langhans W, Maurer V.

Department of Veterinary Parasitology, Research Institute of Organic
Agriculture, Ackerstrasse, 5070 Frick, Switzerland.

Because of the increasing anthelmintic resistance and the impact of conventional
anthelmintics on the environment, it is important to look for alternative
strategies against gastrointestinal nematodes. Phytotherapy could be one of the
major options to control these pathologies. Extracts or ingredients of six
different plant species were tested against exsheathed infective larvae of
Haemonchus contortus using a modified methyl-thiazolyl-tetrazolium (MTT)
reduction assay. Pyrantel tartrate was used as reference anthelmintic.
Bromelain, the enzyme complex of the stem of Ananas comosus (Bromeliaceae), the
ethanolic extracts of seeds of Azadirachta indica (Meliaceae), Caesalpinia
crista (Caesalpiniaceae) and Vernonia anthelmintica (Asteraceae), and the
ethanolic extracts of the whole plant of Fumaria parviflora (Papaveraceae) and
of the fruit of Embelia ribes (Myrsinaceae) showed an anthelmintic efficacy of
up to 93%, relative to pyrantel tartrate. Based on these results obtained with
larval Haemonchus contortus, the modified MTT reduction assay could be a
possible method for testing plant products with anthelmintic properties.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16725288 [PubMed - in process]

32: World J Gastroenterol. 2006 May 7;12(17):2749-55.

Modulatory effects of Azadirachta indica on benzo(a)pyrene-induced forestomach
tumorigenesis in mice.

Gangar SC, Sandhir R, Rai DV, Koul A.

Department of Biophysics, Basic Medical Sciences Block, Panjab University,
Chandigarh, PIN-160014, India.

AIM: To evaluate the chemopreventive effects of aqueous Azadirachta indica (A
indica) leaf extract (AAILE) against benzo(a)pyrene [B(a)P]-induced forestomach
tumorigenesis in Balb/c mice. METHODS: Female Balb/c mice were divided into four
groups of 10-12 animals each. For induction of forestomach tumors, starting from
d 14 of the experi-ment, mice of B(a)P and B(a)P+A indica groups were given
intra-gastric instillations of B(a)P (40 mg/kg), twice a week for four weeks.
Mice of A indica and B(a)P+A indica groups were orally administered with AAILE
(100 mg/kg), two weeks prior to B(a)P instillations till the end of the
experiment. After 22 wk of the first B(a)P instillation, mice were sacrificed
and the forestomachs were analyzed for development of tumors, scanning electron
microscopy (SEM) and histopathology. RESULTS: Tumor incidence was observed to be
100% in mice that received only B(a)P. However, treatment with AAILE reduced the
tumor incidence by 58.4% as observed in mice of B(a)P+A indica group when
compared to that of B(a)P group. Similarly, the tumor burden and multiplicity
were seen to decrease by 87.3% and 69.6% respectively in mice of B(a)P+A indica
group when compared to those of B(a)P group. Scanning electron microscopy
analysis showed that AAILE treatment itself did not cause any abnormalities on
the surface architecture of forestomach epithelium. In tumorous forestomach,
surface disruption was observed. Over the forestomach tumors of B(a)P group of
mice certain rounded structures were seen in addition to closely placed
tongue-shaped squamous cells. Interestingly, these rounded structures were not
observed in B(a)P + A indica group of mice. Histopathalogically, the tumors were
identical and diagnosed to be papillomas. Mice from control and A indica groups
of mice did not develop any forestomach tumors and showed normal
histo-architecture. CONCLUSION: The present data suggest that A indica exerts
chemopreventive effects against B(a)P-induced forestomach tumors in murine
model. Because of lack of toxicity and ubiquitous bioavailability, A indica may
play a promising role in future drug discovery and development as far as
chemoprevention of cancer is concerned.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16718763 [PubMed - indexed for MEDLINE]

33: Can J Microbiol. 2006 May;52(5):427-35.

Fungal endophyte assemblages from ethnopharmaceutically important medicinal

Tejesvi MV, Mahesh B, Nalini MS, Prakash HS, Kini KR, Subbiah V, Shetty HS.

Department of Studies in Applied Botany and Biotechnology, University of Mysore,
Manasagangothri, Karnataka, India.

Endophytic fungi represent an interesting group of microorganisms associated
with the healthy tissues of terrestrial plants. They represent a large reservoir
of genetic diversity. Fungal endophytes were isolated from the inner bark
segments of ethnopharmaceutically important medicinal tree species, namely
Terminalia arjuna, Crataeva magna, Azadirachta indica, Holarrhena
antidysenterica, Terminalia chebula, and Butea monosperma (11 individual trees),
growing in different regions of southern India. Forty-eight fungal species were
recovered from 2200 bark segments. Mitosporic fungi represented a major group
(61%), with ascomycetes (21%) and sterile mycelia (18%) the next major groups.
Species of Fusarium, Pestalotiopsis, Myrothecium, Trichoderma, Verticillium, and
Chaetomium were frequently isolated. Exclusive fungal taxa were recovered from
five of the six plant species considered for the study of endophytic fungi.
Rarefaction indices for species richness indicated the highest expected number
of species for bark segments were isolated from T. arjuna and A. indica (20
species each) and from C. magna (18 species).

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 16699567 [PubMed - indexed for MEDLINE]

34: Immunopharmacol Immunotoxicol. 2006;28(1):33-50.

Prophylactic dose of neem (Azadirachta indica) leaf preparation restricting
murine tumor growth is nontoxic, hematostimulatory and immunostimulatory.

Haque E, Mandal I, Pal S, Baral R.

Department of Immunoregulation and Immunodiagnostics, Chittaranjan National
Cancer Institute, Kolkata, India.

Significant restriction of growth of Ehrlich's carcinoma was observed following
prophylactic treatment on Swiss albino mice with neem leaf preparation (NLP-1
unit) once weekly for four weeks. Toxic effects of this particular dose (1
unit), along with 0.5 unit and 2 units of NLP doses, were evaluated on different
murine physiological systems. One hundred percent of mice could tolerate 4
injections of 0.5 and 1 unit NLP doses. Body weight, different organ-body weight
ratios and physical behavior of treated mice remained completely unchanged
during treatment with different NLP doses. All of these NLP doses were observed
to stimulate hematological systems as evidenced by the increase in total count
of RBC, WBC and platelets and hemoglobin percentage. As histological changes as
well as elevation in serum alkaline phosphatase, SGOT, SGPT were not observed in
mice treated with three different doses of NLP, the nonhepatotoxic nature of NLP
was proved. The level of serum urea remained unaltered and normal architecture
of the cortical and medullary parts of the kidney were also preserved after NLP
treatment. Increased antibody production against B16 melanoma antigen was
detected in mice immunized with 0.5 unit and 1 unit of NLP. Number of splenic T
lymphocytes (CD4+ and CD8+) and NK cells were also observed to be increased in
mice injected with 0.5 unit and 1 unit of NLP. However, NLP dose of 2 units
could not exhibit such immunostimulatory changes; NLP mediated immunostimulation
was correlated well with the growth restriction of murine carcinoma. In other
words, tumor growth restriction was observed only when mice were injected with
immunostimulatory doses of NLP (0.5 unit and 1 unit).

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16684666 [PubMed - indexed for MEDLINE]

35: Mol Cell Biochem. 2006 Jul;287(1-2):69-77. Epub 2006 May 2.

Cytotoxic and antiproliferative effects induced by a non terpenoid polar extract
of A. indica seeds on 3T6 murine fibroblasts in culture.

Di Ilio V, Pasquariello N, van der Esch AS, Cristofaro M, Scarsella G, Risuleo

Biotechnology Biological Control Agency, V. del Bosco, 10--00060 Sacrofano,
Roma, Italy.

Neem oil is a natural product obtained from the seeds of the tree Azadirachta
indica. Its composition is very complex and the oil exhibits a number of
biological activities. The most studied component is the terpenoid azadirachtin
which is used for its insecticidal and putative antimicrobial properties. In
this report we investigate the biological activity of partially purified
components of the oil obtained from A. indica. We show that the semi-purified
fractions have moderate to strong cytotoxicity. However, this is not
attributable to azadirachtin but to other active compounds present in the
mixture. Each fraction was further purified by appropriate extraction procedures
and we observed a differential cytotoxicity in the various sub-fractions. This
led us to investigate the mode of cell death. After treatment with the oil
fractions we observed positivity to TUNEL staining and extensive
internucleosomal DNA degradation both indicating apoptotic death. The
anti-proliferative properties of the neem oil-derived compounds were also
assayed by evaluation of the nuclear PCNA levels (Proliferating Cell Nuclear
Antigen). PCNA is significantly reduced in cells treated with a specific
fraction of neem oil. Finally, our results strongly suggest a possible
involvement of the mitochondrial pathway in the apoptotic death.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16652209 [PubMed - indexed for MEDLINE]

36: Med Princ Pract. 2006;15(3):219-22.

Comparison of free radical scavenging activity of Siamese neem tree (Azadirachta
indica A. Juss var. siamensis Valeton) leaf extracts prepared by different
methods of extraction.

Sithisarn P, Supabphol R, Gritsanapan W.

Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Bangkok,

OBJECTIVE: The aim of this study was to investigate the antioxidant activity of
the aqueous extracts of leaves of Siamese neem tree (Azadirachta indica A. Juss
var. siamensis Valeton) from several extracting and drying methods using
2,2-diphenyl-1-picrylhydrazyl (DPPH)-scavenging assay. MATERIALS AND METHODS:
The leaves of Siamese neem tree were extracted using percolation, decoction,
maceration, soxhlet extraction, freeze drying or spray drying methods. The
extract was tested for antioxidant activity using DPPH-scavenging assay.
Thin-layer chromatography of the extract from decoction was also investigated.
RESULTS: The freeze drying method gave the highest yield (51.50%, w/w) of crude
extract, while decoction gave the most effective DPPH-scavenging activity
(EC(50): 31.4 microg/ml). Thin-layer chromatography analysis was used to screen
the leaf extract obtained using decoction, and the chromatogram showed spots
corresponding to quercetin and rutin flavonoids which exhibited antioxidant
activities (EC(50): 2.29 and 34.67 microg/ml, respectively). CONCLUSION: Siamese
neem tree leaf extracts possessed free radical scavenging activity against the
DPPH radical. The most active extract was obtained with the leaf decoction
method. It showed antioxidant activity with EC(50) of 31.4 microg/ml. Copyright
2006 S. Karger AG, Basel.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16651839 [PubMed - indexed for MEDLINE]

37: In Vivo. 2006 Mar-Apr;20(2):247-51.

Enhancement of immune responses to neem leaf extract (Azadirachta indica)
correlates with antineoplastic activity in BALB/c-mice.

Beuth J, Schneider H, Ko HL.

Institute of Naturopathy, University of Koeln, 50931 Koeln, Germany.
[email protected]

An aqueous plant extract from Azadirachta indica and its chromatographic
fraction F1 (neem extract) exerted immunomodulating and antimetastatic
activities in BALB/ c-mice. Regular subcutaneous administration of neem extract
yielded significantly increased spleen weight and significant enhancement of
peritoneal macrophage activity in the chemiluminescence assay, and activation
marker CD-44 expression. The thymus weight and thymocyte counts did not show
significant differences in the control and neem extract-treated groups, however,
determination of peripheral blood cells revealed significant up-regulations of
leukocyte subsets, the lymphocytes and monocytes. Flow cytometric analaysis of
lymphocyte supopulations documented increased counts of CD-4 and CD-8 cells and
an inreased activation marker expression on lymphocytes (CD-25) and monocytes
(MAC-3) in neem-treated mice compared to the control animals. To evaluate the
antimetastatic activity of neem extract, sarcoma L-1 cells and lymphosarcoma RAW
cells were intravenously inoculated into BALB/c-mice. In these model systems the
number of experimental lung and liver metastases decreased relevantly, however,
biometrically non-significantly in neem extract-treated animals, as compared to
the control mice which received injections of saline solutions. Neem extract can
be regarded as an immunomodulating and antimetastatic substance which holds
promise for further experimental and clinical investigation.

PMID: 16634526 [PubMed - indexed for MEDLINE]

38: Fertil Steril. 2006 Apr;85 Suppl 1:1223-31.

Extract of Azadirachta indica (neem) leaf induces apoptosis in rat oocytes
cultured in vitro.

Chaube SK, Prasad PV, Khillare B, Shrivastav TG.

Department of Reproductive Biomedicine, National Institute of Health and Family
Welfare, New Delhi, India.

OBJECTIVE: To determine whether aqueous neem leaf extract (NLE) could induce
degeneration of rat oocytes and, if so, whether apoptosis is involved during
NLE-induced degeneration of oocytes cultured in vitro. DESIGN: A controlled
prospective study. SETTING: Laboratory research setting at Department of
Reproductive Biomedicine of the Institute. ANIMAL(S): Fifty-four sexually
immature female rats that were 24-25 days of age. INTERVENTION(S): The immature
female rats were injected with 10 IU pregnant mare serum gonadotropin for 48 h
followed by 10 IU human chorionic gonadotropin (hCG) for 16 h. After 16 h, the
rats were killed and ovulated cumulus oocyte complexes were collected from the
oviduct. Cumulus-enclosed as well as denuded oocytes were used in the present
study. MAIN OUTCOME MEASURE(S): Rates of shrinkage, membrane leakage,
degeneration, assessment of morphological apoptotic changes, bax protein
expression, and DNA fragmentation. RESULT(S): The NLE induced morphologic
apoptotic changes such as shrinkage, membrane leakage, and cytoplasmic
fragmentation prior to degeneration of oocytes. The NLE-treated oocytes that had
morphologic apoptotic features showed overexpression of bax protein and DNA
fragmentation as evidenced by terminal deoxynucleotidyl transferase nick-end
labeling-positive staining and DNA ladder pattern. CONCLUSION(S): Neem leaf
extract induced apoptosis in rat oocytes prior to degeneration in vitro.

PMID: 16616096 [PubMed - indexed for MEDLINE]

39: Tree Physiol. 2006 Jul;26(7):899-904.

Interspecific variation in vessel size, growth and drought tolerance of
broad-leaved trees in semi-arid regions of Kenya.

Kondoh S, Yahata H, Nakashizuka T, Kondoh M.

Graduate School of Social and Cultural Studies, Ropponmatsu, Chou-ku, Fukuoka,
810-8560, Japan. [email protected]

In semi-arid regions, trees often wither during the dry season. Withering is
sometimes manifest as die-back, whereby whithering results in shoot death, which
progresses downward from the uppermost part of the crown. In this study, we
measured the relationships between height growth and diameter at breast height,
die-back frequency and severity, vessel size and specific hydraulic conductivity
of four evergreen (Senna siamea (Lamk) H.S. Irwin & Barneby, Jacaranda
mimosifolia D. Don, Azadirachta indica A.H.L. Juss and Acacia gerrardii Benth.)
and one deciduous (Melia volkensii Gurke) plantation tree species in Kenya,
which has a conspicuous dry season. Die-back occurred readily in some species,
but not in others. Senna siamea showed the highest specific hydraulic
conductivity and the highest growth rate among the five species and was quite
susceptible to die-back. Among species, height growth and specific hydraulic
conductivity were positively correlated with vessel size and negatively
correlated with die-back frequency, suggesting a trade-off between growth rate
and drought tolerance. This implies that an adaptation to rapid growth under
humid conditions leads to low drought tolerance. However, the deciduous tree
Melia volkensii showed high specific hydraulic conductivity and growth, with no
symptoms of die-back, implying that a mechanism associated with the deciduous
habit results in drought avoidance by reducing the requirement for water during
the dry season.

PMID: 16585035 [PubMed - in process]

40: Parasitol Res. 2006 Sep;99(4):353-6. Epub 2006 Mar 28.

A new shampoo based on neem (Azadirachta indica) is highly effective against
head lice in vitro.

Heukelbach J, Oliveira FA, Speare R.

Department of Community Health, School of Medicine, Federal University of Ceara,
Fortaleza, Brazil. [email protected]

Because topical compounds based on insecticidal chemicals are the mainstay of
head lice treatment, but resistance is increasing, alternatives, such as herbs
and oils are being sold to treat head lice. To test a commercial shampoo based
on seed extract of Azadirachta indica (neem tree) for its in vitro effect, head
lice (n=17) were collected from school children in Australia and immersed in
Wash-Away Louse shampoo (Alpha-Biocare GmbH, Germany). Vitality was evaluated
for more than 3 h by examination under a dissecting microscope. Positive and
negative controls were a commercially available head lice treatment containing
permethrin 1% (n=19) and no treatment (n=14). All lice treated with the neem
shampoo did not show any vital signs from the initial examination after
immersion at 5-30 min; after 3 h, only a single louse showed minor signs of
life, indicated by gut movements, a mortality of 94%. In the permethrin group,
mortality was 20% at 5 min, 50% at 15 min, and 74% after 3 h. All 14 head lice
of the negative control group survived during the observation period. Our data
show that Wash-Away Louse is highly effective in vitro against head lice. The
neem shampoo was more effective than the permethrin-based product. We speculate
that complex plant-based compounds will replace the well-defined chemical
pediculicides if resistance to the commonly used products further increases.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16568334 [PubMed - in process]

41: J Chem Ecol. 2006 Feb;32(2):325-49. Epub 2006 Mar 23.

Impact of botanical pesticides derived from Melia azedarach and Azadirachta
indica plants on the emission of volatiles that attract Parasitoids of the
diamondback moth to cabbage plants.

Charleston DS, Gols R, Hordijk KA, Kfir R, Vet LE, Dicke M.

Insect Ecology, Agricultural Research Council, Plant Protection Research
Institute, Private Bag X134, Queenswood 0121, South Africa.
[email protected]

Herbivorous and carnivorous arthropods use chemical information from plants
during foraging. Aqueous leaf extracts from the syringa tree Melia azedarach and
commercial formulations from the neem tree Azadirachta indica, Neemix 4.5, were
investigated for their impact on the flight response of two parasitoids, Cotesia
plutellae and Diadromus collaris. Cotesia plutellae was attracted only to
Plutella xylostella-infested cabbage plants in a wind tunnel after an
oviposition experience. Female C. plutellae did not distinguish between P.
xylostella-infested cabbage plants treated with neem and control P.
xylostella-infested plants. However, females preferred infested cabbage plants
that had been treated with syringa extract to control infested plants. Syringa
extract on filter paper did not attract C. plutellae. This suggests that an
interaction between the plant and the syringa extract enhances parasitoid
attraction. Diadromus collaris was not attracted to cabbage plants in a wind
tunnel and did not distinguish between caterpillar-damaged and undamaged cabbage
plants. Headspace analysis revealed 49 compounds in both control cabbage plants
and cabbage plants that had been treated with the syringa extract. Among these
are alcohols, aldehydes, ketones, esters, terpenoids, sulfides, and an
isothiocyanate. Cabbage plants that had been treated with the syringa extract
emitted larger quantities of volatiles, and these increased quantities were not
derived from the syringa extract. Therefore, the syringa extract seemed to
induce the emission of cabbage volatiles. To our knowledge, this is the first
example of a plant extract inducing the emission of plant volatiles in another
plant. This interesting phenomenon likely explains the preference of C.
plutellae parasitoids for cabbage plants that have been treated with syringa

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16555134 [PubMed - indexed for MEDLINE]

42: J Ethnopharmacol. 2006 Jul 19;106(3):403-7. Epub 2006 Mar 13.

Anti-plasmodial activity and toxicity of extracts of plants used in traditional
malaria therapy in Meru and Kilifi Districts of Kenya.

Kirira PG, Rukunga GM, Wanyonyi AW, Muregi FM, Gathirwa JW, Muthaura CN, Omar
SA, Tolo F, Mungai GM, Ndiege IO.

Department of Chemistry, School of Pure & Applied Sciences, Kenyatta University,
P.O. Box 43844, Nairobi 00100 GPO, Kenya.

The methanol and aqueous extracts of 10 plant species (Acacia nilotica,
Azadirachta indica, Carissa edulis, Fagaropsis angolensis, Harrissonia
abyssinica, Myrica salicifolia, Neoboutonia macrocalyx, Strychnos heningsii,
Withania somnifera and Zanthoxylum usambarensis) used to treat malaria in Meru
and Kilifi Districts, Kenya, were tested for brine shrimp lethality and in vitro
anti-plasmodial activity against chloroquine-sensitive and chloroquine-resistant
strains of Plasmodium falciparum (NF54 and ENT30). Of the plants tested, 40% of
the methanol extracts were toxic to the brine shrimp (LD(50)<100micro/ml), while
50% showed in vitro anti-plasmodial activity (IC(50)<100microg/ml). The methanol
extract of the stem bark of N. macrocalyx had the highest toxicity to brine
shrimp nauplii (LD(50) 21.04+/-1.8microg/ml). Methanol extracts of the rest of
the plants exhibited mild or no brine shrimp toxicity (LD(50)>50microg/ml). The
aqueous extracts of N. macrocalyx had mild brine shrimp toxicity (LD(50)
41.69+/-0.9microg/ml), while the rest were lower (LD(50)>100microg/ml). The
methanol extracts of F. angolensis and Zanthoxylum usambarense had IC(50) values
<6microg/ml while the aqueous ones had values between 6 and 15microg/ml, against
both chloroquine-sensitive and resistant P. falciparum strains. The results
support the use of traditional herbs for anti-malarial therapy and demonstrate
their potential as sources of drugs.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16530996 [PubMed - indexed for MEDLINE]

43: Phytother Res. 2006 Mar;20(3):228-31.

Screening of traditional antidiabetic medicinal plants of Mauritius for possible
alpha-amylase inhibitory effects in vitro.

Kotowaroo MI, Mahomoodally MF, Gurib-Fakim A, Subratty AH.

Department of Chemistry, Faculty of Science, University of Mauritius, Reduit,

In this study, seven exotic/indigenous medicinal plants of Mauritius, namely
Coix lacryma-jobi (Poaceae), Aegle marmelos (Rutaceae), Artocarpus heterophyllus
(Moraceae), Vangueria madagascariensis (Rubiaceae), Azadirachta indica
(Meliaceae), Eriobotrya japonica (Rosaceae) and Syzigium cumini (Myrtaceae) were
studied for possible effects on starch breakdown by alpha-amylase in vitro. The
results showed that only Artocarpus heterophyllus significantly (p < 0.05)
inhibited alpha-amylase activity in vitro. To confirm the observed effects, a
further biochemical assay was undertaken to investigate the effects of
Artocarpus heterophyllus on alpha-amylase activity using rat plasma in vitro. It
was found that the aqueous leaf extract significantly (p < 0.05) inhibited
alpha-amylase activity in rat plasma. The highest inhibitory activity (27.20 +/-
5.00%) was observed at a concentration of 1000 microg/mL. However, in both cases
dose dependency was not observed. Enzyme kinetic studies using the
Michaelis-Menten and Lineweaver-Burk equations were performed to establish the
type of inhibition involved. In the presence of the plant extract the maximal
velocity (Vmax) remained constant (1/150 g / L/s) whereas the Michaelis-Menten
constant (Km) increased by 5.79 g / L, indicating that the aqueous leaf extract
of Artocarpus heterophyllus behaved as a competitive inhibitor. Results from the
present study tend to indicate that Artocarpus heterophyllus could act as a
'starch blocker' thereby reducing post-prandial glucose peaks. Copyright 2006
John Wiley & Sons, Ltd.

Publication Types:
Comparative Study

PMID: 16521114 [PubMed - indexed for MEDLINE]

44: Phytother Res. 2006 Mar;20(3):169-77.

Chemomodulatory effects of Azadirachta indica on the hepatic status of skin
tumor bearing mice.

Koul A, Ghara AR, Gangar SC.

Department of Biophysics, Basic Medical Sciences Block, Panjab University,
Chandigarh-160014, India. [email protected]

The liver plays an important role in the modulation of the process of
carcinogenesis, as it is the primary site for the biotransformation of
xenobiotics including carcinogens as well as anticancer drugs. The present study
was designed to evaluate the biochemical alterations occurring in the liver of
7,12-dimethylbenz(a)anthracene (DMBA) induced skin tumor bearing male Balb/c
mice and their modulation by aqueous Azadirachta indica leaf extract (AAILE). It
was observed that skin tumor induction caused hepatic damage characterized by a
decreased hepatosomatic index and significantly increased (p < 0.001) activities
of the hepatic tissue injury marker enzymes, namely alkaline phosphatase,
alanine aminotransferase and aspartate aminotransferase. However, upon treatment
with AAILE, the above-mentioned alterations, including the increased activities
of hepatic tissue injury marker enzymes, were significantly reversed, which
signified the hepato-protective efficacy of Azadirachta indica. Increased
oxidative stress was also observed in the hepatic tissue of skin tumor bearing
mice as revealed by a significant increase (p < 0.001) in lipid peroxidation
levels and a decrease in reduced glutathione contents and activities of various
antioxidant enzymes studied, namely glutathione-S-transferase, glutathione
peroxidase and glutathione reductase. The AAILE treatment reduced oxidative
stress by decreasing lipid peroxidation levels and enhancing the reduced
glutathione contents and activities of various antioxidant enzymes. The
activities of the xenobiotic biotransformation enzymes, namely cytochrome P450,
cytochrome b5 and glutathione-S-transferase, were found to be decreased in the
hepatic tissue of tumor bearing mice. Treatment with AAILE further caused a
decrease in the activity of cytochrome P450 and cytochrome b5, whereas it
up-regulated the activity of glutathione-S-transferase. The significance of
these observations with respect to the progress of the process of carcinogenesis
is explained in the present research article. Copyright 2006 John Wiley & Sons,

Publication Types:
Comparative Study

PMID: 16521106 [PubMed - indexed for MEDLINE]

45: Vet Parasitol. 2006 Apr 30;137(3-4):306-10. Epub 2006 Mar 3.

Anthelmintic activity of Azadirachta indica A. Juss against sheep
gastrointestinal nematodes.

Costa CT, Bevilaqua CM, Maciel MV, Camurca-Vasconcelos AL, Morais SM, Monteiro
MV, Farias VM, da Silva MV, Souza MM.

Faculdade de Veterinaria, Universidade Estadual do Ceara, Av. Parajana 1700,
60740-000 Fortaleza, Ceara, Brazil.

Gastrointestinal nematode control has been performed through use of
anthelmintics. However, the development of resistant populations has required
research into new alternatives. There are popular reports about anti-parasitic
activity of Azadirachta indica in animals and plants. The aim of this study was
to evaluate the anthelmintic activity of A. indica after feeding sheep with the
dried leaves. In this experiment, 40 sheep were allotted into four treatment
groups. Group I received a treatment of A. indica dry leaves mixed in a
concentrate at a rate of 0.1 g/kg dose for 3 months. Group II was treated with
double the dose of Group I. Group III was treated with closantel (Diantel) at
the manufacturer-recommended dose once at the beginning of the study and Group
IV was not treated. To compare treatment effects, the following parameters were
evaluated: egg count per gram of feces (EPG), worm burden, weight gain and
haematocrit. EPG and worm burden results were statistically evaluated using the
Kruskal-Wallis test. Haematocrit and live weight gain were submitted to analysis
of variance (ANOVA) and the means evaluated by Tukey's test with 95%
probability. None of the evaluated parameters of the treatment groups were
statistically different when compared to the control group, demonstrating that,
with the protocol used, A. indica has no anthelmintic effect.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16517074 [PubMed - indexed for MEDLINE]

46: Ann Bot (Lond). 2006 Apr;97(4):667-74. Epub 2006 Feb 7.

Prediction of desiccation sensitivity in seeds of woody species: a probabilistic
model based on two seed traits and 104 species.

Daws MI, Garwood NC, Pritchard HW.

Seed Conservation Department, Royal Botanic Gardens Kew, Wakehurst Place,
Ardingly, West Sussex RH17 6TN, UK. [email protected]

BACKGROUND AND AIMS: Seed desiccation sensitivity limits the ex situ
conservation of up to 47 % of plant species, dependent on habitat. Whilst
desirable, empirically determining desiccation tolerance levels in seeds of all
species is unrealistic. A probabilistic model for the rapid identification of
woody species at high risk of displaying seed desiccation sensitivity is
presented. METHODS: The model was developed using binary logistic regression on
seed trait data [seed mass, moisture content, seed coat ratio (SCR) and rainfall
in the month of seed dispersal] for 104 species from 37 families from a
semi-deciduous tropical forest in Panama. KEY RESULTS: For the Panamanian
species, only seed mass and SCR were significantly related to the response to
desiccation, with the desiccation-sensitive seeds being large and having a
relatively low SCR (i.e. thin 'seed' coats). Application of this model to a
further 38 species, of known seed storage behaviour, from two additional
continents and differing vegetation types (dryland Africa and temperate Europe)
correctly predicted the response to desiccation in all cases, and resolved
conflicting published data for two species (Acer pseudoplatanus and Azadirachta
indica). CONCLUSIONS: This model may have application as a decision-making tool
in the handling of species of unknown seed storage behaviour in species from
three disparate habitats.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16464874 [PubMed - indexed for MEDLINE]

47: J Vector Borne Dis. 2005 Dec;42(4):159-63.

Comparative efficacy of Annona squamosa Linn. and Pongamia glabra Vent. to
Azadirachta indica A. juss against mosquitoes.

George S, Vincent S.

Department of Microbiology, Asan Memorial College, Chennai, India.

PMID: 16457387 [PubMed - indexed for MEDLINE]

48: Mol Cell Biochem. 2006 Feb;283(1-2):47-55.

Inhibitory effects of Azadirachta indica on DMBA-induced skin carcinogenesis in
Balb/c mice.

Koul A, Mukherjee N, Gangar SC.

Department of Biophysics, Basic Medical Sciences Block, Panjab University,
Chandigarh, India. [email protected]

Male Balb/c mice were divided into four groups on the basis of their respective
treatments wherein mice of Group I served as controls. For induction of skin
tumors, mice of Group II and IV were injected sub-cutaneously with
7,12-dimethylbenz(a)anthracene (DMBA). Mice of Group III and IV were
administered aqueous Azadirachta indica leaf extract (AAILE) thrice a week
throughout the experiment. After 14 weeks of the first DMBA injection, Group II
and IV mice developed tumors. In the tumor-bearing mice that received AAILE
(Group IV), a significant reduction in mean tumor burden and tumor volume was
observed. The tumors were confirmed to be papillomas and interestingly, the
extent of hyper-chromatia was observed to be much more in skin tumors of Group
II mice vis a vis the mice receiving AAILE. An increase in the extent of lipid
peroxidation was observed in tumorous tissue of Group IV when compared to that
of Group II mice. Glutathione (GSH) content and the activities of GSH-based
antioxidant enzymes viz. glutathione peroxidase (GPx) and glutathione reductase
(GR) increased significantly in the skin tissues of all the groups of mice when
compared to control counterparts. Catalase activity was found to decrease
significantly in the skin of mice, which received AAILE treatment only (Group
III). Activity of super-oxide dismutase (SOD) decreased significantly in all the
tumorous tissues (Group II and IV mice). In light of the above observations, the
role of AAILE in inhibition of DMBA-induced skin carcinogenesis is discussed in
the present study.

PMID: 16444585 [PubMed - indexed for MEDLINE]

49: Asian Pac J Cancer Prev. 2005 Oct-Dec;6(4):515-20.

Ethanolic neem (Azadirachta indica) leaf extract induces apoptosis in the
hamster buccal pouch carcinogenesis model by modulation of Bcl-2, Bim, caspase 8
and caspase 3.

Subapriya R, Bhuvaneswari V, Nagini S.

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai
University, Annamalainagar 608 002, Tamil Nadu, India.

Induction of apoptosis is one of the most active strategies in cancer
chemoprevention and the ability of medicinal plants in this regard has attracted
major research interest. The present study was designed to investigate the
apoptosis inducing capacity of an ethanolic neem leaf extract (ENLE) during
7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch
carcinogenesis using the apoptosis-associated proteins Bcl-2, Bim, caspase 8 and
caspase 3 as markers. Topical application of DMBA to the hamster cheek pouch for
14 weeks resulted in well developed squamous cell carcinomas associated with
increased expression of Bcl-2 and decreased expression of Bim, caspase 8 and
caspase 3. Administration of ENLE inhibited DMBA-induced hamster buccal pouch
(HBP) carcinogenesis, as revealed by the absence of neoplasms, with induction of
Bim and caspases 8 and 3 and inhibition of Bcl-2 expression. Our results suggest
that the chemopreventive effects of ENLE may be mediated by induction of

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16436003 [PubMed - indexed for MEDLINE]

50: Ann Trop Med Parasitol. 2006 Jan;100(1):17-22.

Fractions of an antimalarial neem-leaf extract have activities superior to
chloroquine, and are gametocytocidal.

Udeinya IJ, Brown N, Shu EN, Udeinya FI, Quakeyie I.

Department of Pharmacology, Howard University College of Medicine, Washington,
DC 20059, USA.

The antimalarial activities of two fractions (IRDN-A and IRDN-B) of an extract
from the leaves of the neem tree (Azadirachta indica) were compared with those
of chloroquine, in in-vitro assays against Plasmodium falciparum. The asexual
stages of a chloroquine-sensitive clone (ITG2F6) and a chloroquine-resistant
isolate (W2) and the gametocytes of the NF 54 (BD-7) isolate of P. falciparum
were used as the drug targets. Activity against the asexual stages was generally
evaluated as the concentrations inhibiting the parasitaemias recorded in the
control cultures, after an incubation of 48-72 h, by 50% (IC50) or 100% (IC100).
For the ITG2F6 strain, the IC50 and IC100 (in microg/ml) were, respectively,
10(-5) and 10(-4) for IRDN-A, 10(-3) and 10(-2) for IRDN-B, and 10(-2) and 1.0
for chloroquine. The corresponding values for the W2 strain were 10(-5) and 1.0
for IRDN-A, and 10.0 and >100 for chloroquine (even at 100 microg/ml,
chloroquine only inhibited the parasitaemia by 85%).Each of the two neem-leaf
fractions lysed 50% and 100% of developing gametocytes, at 10(-3) and 1.0
microg/ml, respectively; and 50% and 100% of mature gametocytes at 10(-3) and
10(2) microg/ml, respectively. If they are found safe and effective in vivo, the
neem-leaf fractions may form the basis of new antimalarial drugs that not only
cure chloroquine-sensitive and chloroquine-resistant malaria but also markedly
reduce transmission.

Publication Types:
Comparative Study

PMID: 16417709 [PubMed - indexed for MEDLINE]

51: Arch Oral Biol. 2006 Jun;51(6):482-90. Epub 2006 Jan 10.

Effect of aqueous extract from Neem (Azadirachta indica A. Juss) on
hydrophobicity, biofilm formation and adhesion in composite resin by Candida

Polaquini SR, Svidzinski TI, Kemmelmeier C, Gasparetto A.

Dentistry Department, University Center of Maringa, Avenida Guedner 1610,
87050-390 Maringa, PR, Brazil.

OBJECTIVE: Azadirachta indica, a Meliaceae family tree, has been used in India
for many years in the treatment of several diseases in medicine and dentistry.
Current research analyses the effects of the leaf aqueous extract from
Azadirachta indica (Neem) on the adhesion, cell surface hydrophobicity and
biofilm formation, which may affect the colonisation by Candida albicans.
METHODS: Azadirachta indica extract was tested in vitro on strains of Candida
albicans 12A and 156B. Changes in hydrophobicity were reported in assays of
yeast adhesion to hydrocarbons, in biofilm formation with glucose and in the
adhesion of the microorganisms on light cured composite resin. Assays involved
enumeration of candidal colony-forming units together with scintillation
counting of radiolabelled Candida and compared to a solution of chlorhexidine
digluconate 0.125% widely used in dentistry. RESULTS: Yeast growth in Neem
extract was not inhibited in concentrations ranging from 0.1mg/ml. A
statistically significant increase (p<0.05) in cell surface hydrophobicity was
evident for the two strain tested and there was also an associated increase in
biofilm formation after contact with Neem extract in concentration 0.01 g/ml.
Decrease in adhesion capacity of cells to composite resin was also recorded.
CONCLUSION: An anti-adhesive mechanism of action by Azadirachta indica is
proposed based on the results observed.

PMID: 16412377 [PubMed - indexed for MEDLINE]

52: Nat Prod Res. 2006 Mar;20(3):241-5.

A new flavanoid from the flowers of Azadirachta indica.

Siddiqui BS, Tariq Ali S, Kashif Ali S.

H.E.J. Research Institute of Chemistry, International Centre for Chemical
Sciences, University of Karachi, Karachi-75270, Pakistan.
[email protected]

Studies on the chemical constituents of the flowers of Azadirachta indica have
led to the isolation of one new flavanone named as azharone
(5,7,4'-trihydroxy-3'-(3''-methyl-2'',3''-epoxybutyl)flavan-4-one (3)) along
with two known constituents azadirone (1), and isoazadironolide (2). Their
structures have been elucidated through spectral studies including 2D-NMR
(COSY-45, NOESY, J-resolved, HMQC, HMBC) experiments.

PMID: 16401554 [PubMed - indexed for MEDLINE]

53: J Ethnopharmacol. 2006 Apr 21;105(1-2):246-50. Epub 2005 Dec 27.

Anticancer effects of ethanolic neem leaf extract on prostate cancer cell line

Kumar S, Suresh PK, Vijayababu MR, Arunkumar A, Arunakaran J.

Department of Biotechnology, Karpagam Arts and Science college, Coimbatore 641
021, India.

Prostate cancer (PC) is the most prevalent cancer and the leading cause of male
cancer death. Azadirachta indica (neem tree) has been used successfully
centuries to reduce tumors by herbalists throughout Southeast Asia. Here the
present study indicated that an ethanolic extract of neem has been shown to
cause cell death of prostate cancer cells (PC-3) by inducing apoptosis as
evidenced by a dose-dependent increase in DNA fragmentation and a decrease in
cell viability. Western blot studies indicated that treatment with neem extract
showed decreased level of Bcl-2, which is anti-apoptotic protein and increased
the level of Bax protein. So the neem extract could be potentially effective
against prostate cancer treatment.

PMID: 16378700 [PubMed - indexed for MEDLINE]

54: East Mediterr Health J. 2004 Jul-Sep;10(4-5):573-81.

Larvicidal activity of a neem tree extract (Neemarin) against mosquito larvae in
the Islamic Republic of Iran.

Vatandoost H, Vaziri VM.

School of Public Health and Institute of Health Research, Tehran University of
Medical Science, Tehran, Islamic Republic of Iran.

An insecticide containing azadirachtin, a neem tree (Azadirachta indica)
extract, was tested against mosquito larvae in the Islamic Republic of Iran
under laboratory and field conditions. LC50 and LC90 values for Neemarin were
0.35 and 1.81 mg/L for Anopheles stephensi, the main local malaria vector, and
0.69 and 3.18 mg/L for Culex quinquefasciatus. The mortality in the pupal stage
was significantly higher than the other stages. In field trials, using
recommended dosages of 1 and 2 L/hectare, mortality of Anopheles spp. larvae was
also higher than Culex spp. Prevention of adult emerged and pupal mortality was
the main activity of this compounds. The maximum time of efficacy was 7 days at
the highest concentration (2 L/hectare).

PMID: 16335649 [PubMed - indexed for MEDLINE]

55: Indian J Exp Biol. 2005 Nov;43(11):1093-103.

Effect of aqueous leaf extract of Azadirachta indica on the reproductive organs
in male mice.

Mishra RK, Singh SK.

Department of Zoology, Banaras Hindu University, Varanasi 221 005, India.

Effect of oral administration (50, 100, and 200 mg/kg body weight/day, for 28
days) of aqucous leaf extract of neem (Azadirachta indica) on the male
reproductive organs of the Parkes (P) strain mice was investigated. The
treatment had no effect on body weight and the reproductive organs weight. In
treated mice, testes showed both normal and affected seminiferous tubules in the
same sections; the affected seminiferous tubules showed intraepithelial
vacuolation, loosening of germinal epithelium, marginal condensation of
chromatin in round spermatids, occurrence of giant cells, mixing of germ cell
types in stages of spermatogenesis and degenerated appearance of germ cells. In
severe cases, the tubules were lined with Sertoli cells only, Sertoli cells and
rare germ cells, or with Sertoli cells and several germ cells but without
cellular association patterns. Also, the frequency of affected seminiferous
tubules in testes of the extract-treated mice was significantly higher than the
controls, though this remained unaffected in mice treated at 50 mg/kg body
weight of the extract. Doses at 50 or 100 mg/kg body weight of neem leaf extract
did not cause appreciable alterations in histological appearance of the
epididymis, while a dose of 200 mg/kg body weight caused marked alterations both
in histological appearance and the level of sialic acid in the duct. The
treatment also had adverse effects on motility, morphology, and number of
spermatozoa in the cauda epididymidis, level of fructose in the seminal vesicle,
and on litter size. After 42 days of withdrawal of the treatment, the
alterations induced in the reproductive organs recovered to control levels. Our
results suggested that treatment with neem leaf extract caused reversible
alterations in the male reproductive organs of P mice.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16313072 [PubMed - indexed for MEDLINE]

56: Mycopathologia. 1998;142(2):81-7.

Evaluation of ash from some tropical plants of Nigeria for the control of
Sclerotium rolfsii Sacc. on wheat (Triticum aestivum L.).

Enikuomehin OA, Ikotun T, Ekpo EJ.

Department of Plant Breeding and Seed Technology, University of Agriculture,
Abeokuta, Ogun State, Nigeria.

Eleven ash samples, from organs of nine tropical plants, were screened for their
abilities to inhibit mycelial growth and sclerotial germination of a Nigerian
isolate of Sclerotium rolfsii on agar and in the soil. Ten ash samples showed
some activity against mycelial growth of S. rolfsii in vitro. Ash samples from
Delonix regia stem wood, Mangifera indica leaf and Vernonia amygdalina leaf were
most effective as each totally inhibited mycelial growth of S. rolfsii in vitro.
Ocimum gratissimum leaf ash, D. regia wood ash and Musa paradisiaca flower bract
ash inhibited sclerotial germination on agar. Nine ash samples protected seeds
against pre-emergence rot. Ash from M. indica leaf, V. amygdalina leaf and
Azadirachta indica leaf protected seedlings against post-emergence infection.
Eichornia crassipes ash, which was ineffective in vitro, offered some protection
to seeds in soil against pre-emergence rot. The study demonstrates potentials of
ash samples from tropical plants in control of S. rolfsii on wheat.

PMID: 16284852 [PubMed]

57: Asian Pac J Cancer Prev. 2005 Jul-Sep;6(3):263-9.

Quinone reductase inducers in Azadirachta indica A. Juss flowers, and their
mechanisms of action.

Sritanaudomchai H, Kusamran T, Kuakulkiat W, Bunyapraphatsara N, Hiransalee A,
Tepsuwan A, Kusamran WR.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok,

We have previously shown that the flowers of neem tree (Azadirachta indica A.
Juss, family Meliaceae), Thai variety, strongly induced the activity of
glutathione S-transferase (GST) while resulting in a significant reduction in
the activities of some cytochrome P(450)-dependent monooxygenases in rat liver,
and possess cancer chemopreventive potential against chemically-induced mammary
gland and liver carcinogenesis in rats. In the present study, 2 chemicals
possessing strong QR inducing activity were fractionated from neem flowers using
a bioassay based on the induction of QR activity in mouse hepatoma Hepa 1c1c7
cultured cells. Spectroscopic characteristics revealed that these compounds were
nimbolide and chlorophylls, having CD (concentration required to double QR
specific activity) values of 0.16 and 3.8 mug/ml, respectively. Nimbolide is a
known constituent of neem leaves, but was found for the first time here in the
flowers. Both nimbolide and chlorophylls strongly enhanced the level of QR mRNA
in Hepa 1c1c7 cells, as monitored by northern blot hybridization, indicating
that the mechanism by which these constituents of neem flowers induced QR
activity is the induction of QR gene expression. These findings may have
implication on cancer chemopreventive potential of neem flowers in experimental
rats previously reported.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16235984 [PubMed - indexed for MEDLINE]

58: J Biosci Bioeng. 2003;96(1):16-22.

Necessity of a two-stage process for the production of azadirachtin-related
limonoids in suspension cultures of Azadirachta indica.

Raval KN, Hellwig S, Prakash G, Ramos-Plasencia A, Srivastava A, Buchs J.

Dept. of Biochemical Eng. & Biotech., Indian Institute of Technology Delhi, New
Delhi 110016, India.

The effect of major nutrients on growth and azadirachtin-related limonoids
(AZRL) production in plant cell culture of Azadirachta indica (neem) was studied
with the objective to increase the yield of AZRL, one of the major group of
pesticidal compounds found in intact neem trees. We report the novel online
monitoring of plant cell respiration activities in a new parallel shake flask
measuring device. Results obtained using three standard plant cell culture media
showed non-growth-associated production characteristics for AZRL. These findings
were supported by the oxygen uptake rate data. Further investigations on AZRL
production in a modified MS medium with different concentrations of nitrogen and
phosphorus sources resulted in 0.25 mg.g(-1) dry weight of AZRL, compared to no
detectable AZRL production in standard MS media. These characteristics suggest
the necessity of a two-stage process for the production of AZRL in plant cell
culture. Compared to the single-stage process, an almost twofold increase in the
volumetric productivity of AZRL was achieved using the two-stage process.

PMID: 16233477 [PubMed]

59: Phytother Res. 2005 Sep;19(9):792-5.

Concurrent administration of aqueous Azadirachta indica (neem) leaf extract with
DOCA-salt prevents the development of hypertension and accompanying
electrocardiogram changes in the rat.

Obiefuna I, Young R.

Department of Basic Medical Sciences, University of the West Indies.
[email protected]

The effect of concurrent administration of Azadirachta indica leaf extract with
DOCA-salt was investigated in the development of hypertension.Over 5-6 week old,
inbred male Wistar rats with a starting weight of 190 g were given either: (1)
twice weekly subcutaneous (s.c.) injections of vehicle (soyabean oil, 0.25 mL
per animal) for the first 2 weeks, plus normal drinking water (controls); (2)
twice weekly (s.c.) injections (weeks 1 and 2 only) of 15 mg/kg DOCA dissolved
in vehicle, plus drinking water containing 1.0% NaCl and 0.03% KCl (DOCA-salt
group); or (3) 20 mg/kg of aqueous neem extract daily, in addition to the
DOCA-salt treatment (DOCA-salt-neem group). All groups (8-12 animals) received
normal rat pellets ad libitum and their BP was measured weekly. Terminally, the
animals were anaesthetized and ECGs recorded using s.c. pins in a lead II
configuration.The mean arterial pressure was significantly lower (p < 0.05) in
the control (97 +/- 3.7 mmHg) and DOCA-salt-neem (87 +/- 3.4 mm Hg) groups than
in the DOCA-salt group (115 +/- 7.1 mm Hg). PR and RR intervals and the duration
of the QRS complex were shorter (p < 0.05) in the DOCA-salt group than in the
control and DOCA-salt-neem groups. Amplitude of the QRS complex was increased (p
< 0.05) in the DOCA-salt group compared with both the DOCA-salt-neem and the
control groups.Daily administration of 20 mg/kg neem-leaf extract concurrently
with DOCA-salt for 5 weeks, prevents the development of hypertension and the
accompanying alterations in the ECG patterns seen in DOCA-salt treated rats.
Copyright 2005 John Wiley & Sons, Ltd.

PMID: 16220573 [PubMed - indexed for MEDLINE]

60: Phytother Res. 2005 Sep;19(9):756-66.

Ultrastructural changes in Leydig cells and cauda epididymal spermatozoa induced
by Azadirachta indica leaves in albino rats.

Aladakatti RH, Ahamed RN.

Department of Post-Graduate Studies and Research in Zoology, Karnatak
University, Dharwad, India.

The effects of Azadirachta indica leaves (500 mg/kg body weight, orally/day),
testosterone (0.25 mg/kg body weight/day, intramuscularly) and a combination of
these two were investigated as to whether Azadirachta indica leaves affect the
morphology of Leydig cells and epididymal sperm and their organelles at the
ultrastructural level. Azadirachta indica treated rats showed atrophic
seminiferous tubules with widening intercellular spaces. Leydig cells exhibited
characteristics of degeneration such as indented nuclei; the commencement of
degeneration was evident from less chromatin; the reduced amount of a marked
decrease in organelle content and scarcity of other cell types of the
interstitium in highly vacuolated cytoplasm, which were seem from both light and
electron microscopic observations. The number of Leydig cells and their nuclear
diameter were reduced significantly. Pathological changes in the spermatozoa of
the cauda epididymis were observed and the spermatozoa retained cytoplasmic
droplets. It is suggested that regression of Leydig cells and the absence of
interstitium cell types indicates an androgen deficiency, which affects the
spermatozoa in the epididymis by disturbing the internal epididymal milieu. The
antiandrogenic and antispermatogenic properties of Azadirachta indica leaves
appear to lead to a reduced fertilizing ability of the sperm. Copyright 2005
John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16220567 [PubMed - indexed for MEDLINE]

61: Bull Entomol Res. 2005 Oct;95(5):457-65.

Behavioural responses of diamondback moth Plutella xylostella (Lepidoptera:
Plutellidae) to extracts derived from Melia azedarach and Azadirachta indica.

Charleston DS, Kfir R, Vet LE, Dicke M.

Insect Ecology, Agricultural Research Council, Plant Protection Research
Institute, Private Bag X134, Queenswood 0121, South Africa.
[email protected]

The impact of three different doses of botanical insecticide derived from the
syringa tree, Melia azedarach and the neem tree, Azadirachta indica was tested
on the behaviour of the diamondback moth, Plutella xylostella (Linnaeus). Both
botanical insecticides had a significant impact on larval behaviour. At higher
doses the extracts showed feeding deterrent activity, with larvae preferring the
untreated sides of cabbage leaves and consuming less of the treated half of
cabbage leaves. The botanical insecticides had less of an effect on the
oviposition behaviour of P. xylostella moths. In laboratory and glasshouse
trials, significantly fewer eggs were oviposited on the plants that had been
treated with syringa extracts. Therefore, the syringa extracts appear to have a
repellent effect. In contrast, when exposed to the neem extracts the moths did
not discriminate between control plants and treated plants. Behavioural
observation indicated that, despite the lower number of eggs oviposited on
cabbage treated with syringa extracts, the moths chose cabbage treated with the
highest dose of syringa more often than they chose control cabbage plants.
Similar observations were found in cabbage plants treated with neem, moths chose
the medium dose more often than they chose the control. Oviposition and feeding
deterrent properties are important factors in pest control, and results from
this study indicate that botanical insecticides have the potential to be
incorporated into control programmes for P. xylostella in South Africa.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16197566 [PubMed - indexed for MEDLINE]

62: Chemosphere. 2006 Mar;62(8):1381-7. Epub 2005 Sep 27.

The toxicity and behavioural effects of neem limonoids on Cnaphalocrocis
medinalis (Guenee), the rice leaffolder.

Senthil Nathan S, Kalaivani K, Sehoon K, Murugan K.

Department of Environmental Engineering, Chonbuk National University, 664-14 1ga
Duckjin-Dong Duckjin, Jeonju City, Chola buktho, Chonbuk 561 756, Republic of
Korea. [email protected]

Meliaceae plant products have been shown to exert pesticidal properties against
a variety of insect species. In agricultural pest control programs, such
products may have the potential to be used successfully as botanical
insecticides. The effect of the neem (Azadirachta indica) limonoids
azadirachtin, salannin, deacetylgedunin, gedunin, 17-hydroxyazadiradione and
deacetylnimbin on the biology and mortality of rice leaffolder larvae was
investigated. In laboratory experiments, treatment with neem limonoids
suppressed leaf folding behaviour of C. medinalis. Biological parameters (larval
duration, pupal duration adult longevity and fecundity) were also affected by
the treatment. Azadirachtin, salannin, and deacetylgedunin showed high
bioactivity at all doses, while the rest of the neem limonoids were less active,
and were only biologically active at high doses. Azadirachtin was most potent in
all experiments and produced almost 100% larval mortality at 1 ppm
concentration. These results indicate neem limonoids affect the larval
behaviour. These effects are most pronounced in early instars.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16194558 [PubMed - indexed for MEDLINE]

63: J Basic Clin Physiol Pharmacol. 2005;16(1):67-80.

Changes in Sertoli cells of albino rats induced by Azadirachta indica A. Juss

Aladakatti RH, Ahamed RN.

Department of Post-Graduate Studies & Research in Zoology Karnatak University,
Dharwad 580003, India.

Azadirachta indica leaf powder, 0.05 mg testosterone, or combined leaf powder +
testosterone was administered for 48 days to different groups of 3-month-old
albino rats. Twenty-four hours after the final dose, the treated animals
received mild ether anesthesia and the testes were dissected out and processed
for light and electron microscope studies. Animals treated with A. indica leaf
powder showed damaged tubules and exhibited an abundance of vacuoles, including
inter-cellular spaces and intra-epithelial vacuoles of varying size in the
cytoplasm of Sertoli cells. Upon treatment with A. indica leaf powder, bridges
between Sertoli cells-Sertoli cells and Sertoli cell-germ cells were disturbed,
coupled with changes in the Sertoli cells and cytoplasm along with its
organelles. We suggest that the anti-androgenic property of A. indica leaves
probably affects Sertoli cells, followed by the degeneration of germ cells,
resulting in exfoliation.

PMID: 16187487 [PubMed - indexed for MEDLINE]

64: Mol Cell Biochem. 2005 Oct;278(1-2):177-84.

Effect of herbal polyphenols on atherogenic transcriptome.

Kaul D, Shukla AR, Sikand K, Dhawan V.

Department of Experimental Medicine & Biotechnology, Postgraduate Institute of
Medical Education and Research, Chandigarh, India. [email protected]

The ancient Indian system of medicine supports the antiatherogenic properties of
some herbs. The crosstalk amongst the genes coding for LDLR, LXRalpha, PPARs
(alpha,gamma), CD-36 and c-myc may be important in atherogenesis because these
genes control lipid metabolism, cytokine production and cellular activity within
the arterial wall. Hence, we attempted for the first time to explore whether or
not the polyphenols extracted from medicinal herbs had any effect on the
transcription of these genes. Normal human mononuclear cells were cultured in
the presence of polyphenols (and their HPLC purified sub-fractions) extracted
from Green tea (Camellia sinensis), Neem (Azadirachta indica) and Tulsi (Ocimum
sanctum). Transcriptional expression of these genes was measured by using RT-PCR
and SCION IMAGE analysis software. These polyphenolic extracts were found to
have the inherent capacity to inhibit the transcriptional expression of genes
having direct involvement in atherogenic process. On the basis of these results,
we propose for the first time that HPLC purified polyphenolic fraction IV of
Tulsi may have a profound antiatherogenic effect.

PMID: 16180103 [PubMed - indexed for MEDLINE]

65: Sci Total Environ. 2006 Jul 1;364(1-3):200-14. Epub 2005 Sep 16.

Antimutagenic effect of neem leaves extract in freshwater fish, Channa punctatus
evaluated by cytogenetic tests.

Farah MA, Ateeq B, Ahmad W.

Gene-Tox Lab, Section of Genetics, Department of Zoology, Aligarh Muslim
University, Aligarh-202002, India. [email protected]

Neem (Azadirachta indica), an indigenous plant commonly grown in India and its
sub-continent is a multipurpose plant well known for its insecticidal and
biomedical properties, however, its antimutagenic effects in vertebrate
organisms are lacking. The present work is therefore, focused on possible
antimutagenic potential of ethanolic extract of neem leaves evaluated on the
clastogenicity induced by Pentachlorophenol (PCP) and 2, 4-dichlorophenoxyacetic
acid (2,4-D) in freshwater fish, Channa punctatus used as a vertebrate model, by
cytogenetic endpoints: chromosome aberration (CA) and micronucleus (MN) test. In
the first set of experiment, fish were exposed by medium treatment to a single
treatment of each chemical (PCP, 0.6 ppm; 2,4-D, 75 ppm; neem extract, 3 ppm)
along with the controls. The chromosome preparations were made after processing
kidney cells and micronucleus slides were prepared from peripheral blood at
multiple duration (48, 72 and 96 h). PCP and 2,4-D when used alone, induced
significant CA and MN in a time dependent manner. Neem extract did not show
genotoxic potential in both assays. The maximum frequency of CA were recorded as
18.58% and 15.17%, while frequency of MN reached to 8.08% and 4.62% by PCP and
2,4-D respectively, after 96 h exposure. In the second set of experiment, three
concentrations of neem extract (1, 2 and 3 ppm) were run simultaneously with the
same concentration of PCP (0.6 ppm) and 2,4-D (75 ppm) for antimutagenicity
estimates. In mixed treatment, neem extract significantly reduced the frequency
of CA and MN. The reduction in the frequency of CA ranged from 40-75% and
45.4-83.3% and similar values for MN were 40.2-75.3% and 44.1-65.8% for PCP and
2,4-D respectively. Although the reductions were significant but not dependent
on concentration and time intervals employed. Results suggested that under
present experimental conditions, neem extract exhibit strong antimutagenic
activity in this fish model, which could further contribute to study its benefit
in humans.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16169061 [PubMed - indexed for MEDLINE]

66: Chemosphere. 2006 Mar;62(8):1388-93. Epub 2005 Sep 12.

Effect of neem limonoids on lactate dehydrogenase (LDH) of the rice leaffolder,
Cnaphalocrocis medinalis (Guenee) (Insecta: Lepidoptera: Pyralidae).

Senthil Nathan S, Kalaivani K, Chung PG, Murugan K.

Department of Environmental Engineering, Chonbuk National University, 664-14 1ga
Duckjin-Dong Duckjin, Jeonju City, Chola buktho, Chonbuk 561 756, Republic of
Korea. [email protected]

Neem is derived from the neem tree Azadirachta indica A. Juss. (Meliaceae), and
its primary insecticidal component is the tetranortriterpenoid azadirachtin and
other limonoids. The effect of neem limonoids azadirachtin, salannin,
deacetylgedunin, gedunin, 17-hydroxyazadiradione and deacetylnimbin on enzyme
lactate dehydrogenase (LDH) activity of the rice leaffolder (RLF) Cnaphalocrocis
medinalis (Lepidoptera: Pyralidae) larvae was investigated. There was a decrease
in enzyme activity relative to the control at all concentrations tested. When
fed a diet of rice leaves treated with neem limonoids in bioassays, gut tissue
enzyme, LDH levels in rice leaffolder larvae are affected. These results
indicate neem limonoids affect LDH activity. These effects are most pronounced
in early instar larvae. Azadirachtin was the most potent in of all the limonoids
in all experiments indicating strong enzyme inhibition. Clear dose-response
relationships were established with respect to LDH activity.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16154614 [PubMed - indexed for MEDLINE]

67: Acta Trop. 2005 Oct;96(1):47-55.

Effects of neem limonoids on the malaria vector Anopheles stephensi Liston
(Diptera: Culicidae).

Nathan SS, Kalaivani K, Murugan K.

Department of Environmental Engineering, Chonbuk National University, Jeonju
City, South Korea. [email protected]

The effects of the neem (Azadirachta indica A. Juss) limonoids azadirachtin,
salannin, deacetylgedunin, gedunin, 17-hydroxyazadiradione and deacetylnimbin on
Anopheles stephensi Liston (Diptera: Culicidae) were investigated. In exploring
advantages of pure neem limonoids, we studied the larvicidal, pupicidal,
adulticidal and antiovipositional activity of neem limonoids. Azadirachtin,
salannin and deacetylgedunin showed high bioactivity at all doses, while the
rest of the neem limonoids were less active, and were only biologically active
at high doses. Azadirachtin was the most potent in all experiments and produced
almost 100% larval mortality at 1 ppm concentration. In general, first to third
larval instars were more susceptible to the neem limonoids. Neem products may
have benefits in mosquito control programs.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16112073 [PubMed - indexed for MEDLINE]

68: Phytother Res. 2005 May;19(5):409-15.

Effect of Dianex, a herbal formulation on experimentally induced diabetes

Mutalik S, Chetana M, Sulochana B, Devi PU, Udupa N.

College of Pharmaceutical Sciences, Manipal, Karnataka, India.

Dianex, a polyherbal formulation consisting of the aqueous extracts of Gymnema
sylvestre, Eugenia jambolana, Momordica charantia Azadirachta indica, Cassia
auriculata, Aegle marmelose, Withania somnifera and Curcuma longa was screened
for hypoglycemic activity in normal and streptozotocin induced diabetic mice.
Dianex was administered in different doses of 100-500 mg/kg/day orally in acute
(6 h) and long-term (6 weeks) studies. Blood glucose levels were checked 2-6 h
after treatment in acute studies and every 2 weeks in long-term studies. Body
weight was recorded on the first and final day of the treatment in the long-term
studies with diabetic mice. After 6 weeks, high-density lipoprotein,
triglycerides, total cholesterol, alanine transaminase (ALT), aspertate
transaminase (AST), urea and creatinine were estimated in serum of the diabetic
mice. Glycogen and total protein levels were estimated in the liver. Also, the
liver and pancreas was subjected to histological examination. Oral glucose
tolerance and in vitro free radical scavenging activity was also studied.Dianex
produced significant (p<0.05) hypoglycemic activity at 250-500 mg/kg doses in
both normal and diabetic mice in acute and long-term studies. The body weight of
diabetic mice significantly (p<0.05) increased with all tested doses of Dianex.
The elevated triglycerides, cholesterol, ALT, AST, urea and creatinine levels in
diabetic mice were significantly (p<0.05) reduced at the doses of 250 and 500
mg/kg. The liver glycogen and protein levels were both significantly (p<0.05)
increased in diabetic mice at 250 and 500 mg/kg doses. Dianex increased the
glucose tolerance significantly (p<0.05) in both normal and diabetic mice at all
the doses tested. Histopathological examination showed that the formulation
decreased streptozotocin induced injury to the tissues at all the doses tested.
It produced significant (p<0.05) free radical scavenging activity against ABTS+,
DPPH and hydroxyl free radicals at the concentrations ranging between 10-1000
microg/ml.Thus, in the present study, Dianex produced significant hypoglycemic
activity in both normal and diabetic animals. It also reversed other diabetic
complications in diabetic mice at 250 and 500 mg/kg doses. In our earlier study,
Dianex was well tolerated in laboratory animals at higher doses (upto 10 g/kg in
mice, acute toxicity; up to 2.5 g/kg in rats, subacute toxicity studies for 30
days) without exhibiting any toxic manifestation. Hence, Dianex may be useful in
the treatment of diabetes mellitus. Copyright (c) 2005 John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16106394 [PubMed - indexed for MEDLINE]

69: J Herb Pharmacother. 2005;5(1):35-43.

Phenolic acids in neem (Azadirachta indica): a major pre-existing secondary

Singh UP, Maurya S, Singh DP.

Department of Mycology and Plant Pathology, Banaras Hindu University, Varanasi
221005, India. [email protected]

High Performance Liquid Chromatographic (HPLC) analyses of various parts (fresh
and dry bark of stem, mature and tender leaves, flower and different parts of
fruit, i.e., raw and ripe fruit epicarp, mesocarp and seed) of neem (Azadirachta
indica), which occupies an important place in socio-cultural-religious life in
Indian communities, indicate that neem is rich in pre-existing secondary
metabolites (phenolic acids). Dry bark showed only tannic acid but in fresh bark
three phenolic acids were observed, i.e., gallic, tannic, and ferulic acids. In
tender leaves only gallic and ferulic acids were detected, but the levels of
these phenolic acids in mature leaves were about three times and fifty times
greater, respectively. Flowers had only two phenolic acids in which gallic acid
was maximum followed by chlorogenic acid. The level of phenolic acid was maximum
in seeds followed by epicarp and pulp. In raw and ripe fruit seeds four phenolic
acids were detected. Raw fruit seeds were rich in phenolic acids than ripe fruit
seeds. Fruit epicarp was relatively richer than seed, seed pulp and flowers of
the plants. Neem flowers were also rich in gallic and chlorogenic acids.

PMID: 16093234 [PubMed - indexed for MEDLINE]

70: Trans R Soc Trop Med Hyg. 2005 Oct;99(10):769-74.

Phase I safety study of Praneem polyherbal vaginal tablet use among
HIV-uninfected women in Pune, India.

Joshi SN, Katti U, Godbole S, Bharucha K, B KK, Kulkarni S, Risbud A, Mehendale

National AIDS Research Institute, Epidemiology Department, MIDC, Bhosari, Pune,
Maharashtra, India. [email protected]

Praneem polyherbal formulations containing purified extracts of Azadirachta
indica (neem tree) have shown activity against HIV and sexually transmitted
disease pathogens in studies in vitro. The product also has contraceptive
properties. This has prompted its development as a possible microbicide. We
evaluated the safety of Praneem polyherbal tablet use among HIV-uninfected
women. Twenty eligible women were enrolled in a Phase I open-label study
requiring 14 days of consecutive intravaginal use of Praneem polyherbal tablets.
Nine (45%) participants experienced 17 episodes of genital irritation. Transient
genital itching was reported by eight (40%) participants, burning micturation by
two (10%) and lower abdominal pain, genital burning and intermenstrual spotting
by one (5%) each. On colposcopy, petechial haemorrhage was observed in two
participants, one on day 7 and the other on day 14, and both were resolved
without any treatment. There were no serious adverse events. Praneem polyherbal
tablets were found to be safe for once daily intravaginal use for 14 consecutive
days in sexually active HIV-uninfected women and a Phase II study may be taken
up as a priority.

Publication Types:
Clinical Trial, Phase I

PMID: 16084547 [PubMed - indexed for MEDLINE]

71: J Zhejiang Univ Sci B. 2005 Aug;6(8):736-42.

Studies on the management of root-knot nematode, Meloidogyne incognita-wilt
fungus, Fusarium oxysporum disease complex of green gram, Vigna radiata cv

Haseeb A, Sharma A, Shukla PK.

Department of Plant Protection, Faculty of Agricultural Sciences, Aligarh Muslim
University, Aligarh-202002, India. [email protected]

Studies were conducted under pot conditions to determine the comparative
efficacy of carbofuran at 1 mg a.i./kg soil, bavistin at 1 mg a.i./kg soil, neem
(Azadirachta indica) seed powder at 50 mg/kg soil, green mould (Trichoderma
harzianum) at 50.0 ml/kg soil, rhizobacteria (Pseudomonas fluorescens) at 50.0
ml/kg soil against root-knot nematode, Meloidogyne incognita-wilt fungus,
Fusarium oxysporum disease complex on green gram, Vigna radiata cv ML-1108. All
the treatments significantly improved the growth of the plants as compared to
untreated inoculated plants. Analysis of data showed that carbofuran and A.
indica seed powder increased plant growth and yield significantly more in
comparison to bavistin and P. fluorescens. Carbofuran was highly effective
against nematode, bavistin against fungus, A. indica seed powder against both
the pathogens and both the bioagents were moderately effective against both the

Publication Types:
Comparative Study

PMID: 16052706 [PubMed - indexed for MEDLINE]

72: Ecotoxicol Environ Saf. 2006 Sep;65(1):102-7. Epub 2005 Jul 19.

Effect of biopesticides on the lactate dehydrogenase (LDH) of the rice
leaffolder, Cnaphalocrocis medinalis (Guenee) (Insecta: Lepidoptera: Pyralidae).

Nathan SS, Kalaivani K, Murugan K.

Department of Environmental Engineering, Chonbuk National University, Jeonju
City, Chonbuk 561 756, South Korea. [email protected]

The effects of bacterial toxins (Bacillus thuringiensis) and botanical
insecticides (Azadirachta indica and Vitex negundo) on lactate dehydrogenase
(LDH) activity in Cnaphalocrocis medinalis (Guenee) (the rice leaffolder) were
evaluated. Bacterial toxins and botanical insecticides affected the LDH activity
individually and in combination. When they were combined, the effect was more
severe at low concentration. There was a decrease in enzyme activity over
controls at all concentrations tested. The combined effect of the three
biopesticides resulted in a considerable decrease in enzyme activity, indicating
strong enzyme inhibition. Clear dose-response relationships were established
with respect to enzyme activity.

PMID: 16033698 [PubMed - indexed for MEDLINE]

73: Mycopathologia. 2005 Jun;159(4):565-70.

Morphological alterations in toxigenic Aspergillus parasiticus exposed to neem
(Azadirachta indica) leaf and seed aqueous extracts.

Razzaghi-Abyaneh M, Allameh A, Tiraihi T, Shams-Ghahfarokhi M, Ghorbanian M.

Department of Mycology, Pasteur Institute of Iran, 13164, Tehran, IR Iran.

The mode of action of the extracts prepared from neem plant i.e., Azadirachta
indica on aflatoxin formation in toxigenic Aspergillus species is not well
understood. Aflatoxin production by A. parasiticus was suppressed depending on
the concentration of the plant aqueous extract (0, 1.56, 3.12, 6.25, 12.5, and
50% v/v) added to the culture media at the time of spore inoculation. Aflatoxin
production in fungal mycelia grown for 96 h in culture media containing 50% neem
leaf and seed extracts was inhibited by approximately 90 and approximately 65%
respectively. Under similar conditions, culture media amended with 1.56% of leaf
or seed extract caused approximately 23 and approximately 7% inhibition
respectively. Mycelial samples exposed to selected concentrations of the plant
extract (1.56 or 50% v/v) collected and processed for morphological studies.
Semi-thin longitudinal and cross sections prepared from control (untreated) and
treated mycelia (1.56% v/v) revealed that alterations are limited to the
vacuolation of the mycelial cytoplasm. Nevertheless, exposure to high
concentration i.e., 50% v/v of the extract resulted in vacuolation of the
mycelial cytoplasm and vesicle deformation causing attenuation of cell wall at
variable intervals. Herniation of the cytoplasmic contents that was protruding
from the mycelium was associated with deformation of the mycelium. Some mycelia
showed a cleft between the cell wall and cytoplasm. Association of aflatoxin
production with morphological changes suggest that probably integrity of the
cell barriers particularly cell wall is critical in regulation of aflatoxin
production and excretion.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15983743 [PubMed - indexed for MEDLINE]

74: J Hazard Mater. 2005 Oct 17;125(1-3):102-12.

Azadirachta indica (Neem) leaf powder as a biosorbent for removal of Cd(II) from
aqueous medium.

Sharma A, Bhattacharyya KG.

Department of chemistry, Gauhati University, Guwahati 781014, Assam, India.

A biosorbent, Neem leaf powder (NLP), was prepared from the mature leaves of the
Azadirachta indica (Neem) tree by initial cleaning, drying, grinding, washing to
remove pigments and redrying. The powder was characterized with respect to
specific surface area (21.45 m2g(-1)), surface topography and surface functional
groups and the material was used as an adsorbent in a batch process to remove
Cd(II) from aqueous medium under conditions of different concentrations, NLP
loadings, pH, agitation time and temperature. Adsorption increased from 8.8% at
pH 4.0 to 70.0% at pH 7.0 and 93.6% at pH 9.5, the higher values in alkaline
medium being due to removal by precipitation. The adsorption was very fast
initially and maximum adsorption was observed within 300 min of agitation. The
kinetics of the interactions was tested with pseudo first order Lagergren
equation (mean k(1)=1.2x10(-2)min(-1)), simple second order kinetics (mean
k2=1.34x10(-3) gmg(-1)min(-1)), Elovich equation, liquid film diffusion model
(mean k=1.39x10(-2)min(-1)) and intra-particle diffusion mechanism. The
adsorption data gave good fits with Langmuir and Freundlich isotherms and
yielded Langmuir monolayer capacity of 158mgg(-1) for the NLP and Freundlich
adsorption capacity of 18.7 Lg(-1). A 2.0 g of NLP could remove 86% of Cd(II) at
293 K from a solution containing 158.8 mg Cd(II) per litre. The mean values of
the thermodynamic parameters, DeltaH, DeltaS and DeltaG, at 293 K were -73.7
kJmol(-1), -0.24 Jmol(-1)K(-1) and -3.63 kJmol(-1), respectively, showing the
adsorption process to be thermodynamically favourable. The results have
established good potentiality for the Neem leaf powder to be used as a
biosorbent for Cd(II).

Publication Types:
Evaluation Studies

PMID: 15961221 [PubMed - indexed for MEDLINE]

75: Braz J Med Biol Res. 2005 Jun;38(6):943-7. Epub 2005 Jun 1.

Extracts of Azadirachta indica and Melia azedarach seeds inhibit
folliculogenesis in albino rats.

Roop JK, Dhaliwal PK, Guraya SS.

Department of Zoology and Fisheries, Punjab Agricultural University, Ludhiana,
Punjab, India. [email protected]

The seed oil of Azadirachta indica A. Juss (neem) is used in traditional
medicine for its antidiabetic, spermicidal, antifertility, antibacterial, and
wound healing properties. The present study was undertaken to investigate the
quantitative aspects of follicular development in cyclic female albino rats (135
+/- 10 g; 8 groups with 6 animals in each group) after oral administration of
polar (PF) and non-polar (NPF) fractions of A. indica seed extract at 3 and 6 mg
kg body weight-1 day-1 and Melia azedarach Linn. (dharek) seed extract at 24 mg
kg body weight-1 day-1 for 18 days. The extracts were prepared using a flash
evaporator at 35 degrees C and then dissolved in olive oil to prepare doses on a
per kg body weight basis. There was a significant reduction (P = 0.05) in the
number of normal single layered follicles (A. indica: 0.67 +/- 0.33 and 4.67 +/-
2.03 after 3 and 6 mg/kg NPF, and 3.33 +/- 1.67 and 1.00 +/- 1.00 after 3 and 6
mg/kg PF vs control: 72.67 +/- 9.14 and M. azedarach: 0.60 +/- 0.40 and 1.80 +/-
1.2 after 24 mg/kg PF and NPF, respectively, vs control: 73.40 +/- 7.02) and
follicles in various stages (I-VII) of follicular development in all treatment
groups. These extracts also significantly reduced (P = 0.05) the total number of
normal follicles in the neem (14.67 +/- 5.93 and 1.00 +/- 1.00 after 3 and 6
mg/kg PF and 3.67 +/- 0.88 and 5.33 +/- 2.03 after 3 and 6 mg/kg NPF) and dharek
(13.00 +/- 3.58 and 14.60 +/- 2.25 after 24 mg/kg NPF and PF) treatments
compared to control (216.00 +/- 15.72 and 222.20 +/- 19.52, respectively).
Currently, indiscriminate use of persistent and toxic rodenticides to control
rodent populations has created serious problems such as resistance and
environmental contamination. Therefore, it becomes necessary to use ecologically
safe and biologically active botanical substances that are metabolized and are
not passed on to the next trophic level, and that interfere with the
reproductive potential particularly growth and differentiation of follicles.
This may help elevate the socio-economic status of the country. Thus, the
present study is an attempt to investigate the effects of A. indica and M.
azedarach seed extracts on reproduction of albino rats.

PMID: 15933789 [PubMed - indexed for MEDLINE]

76: Odontostomatol Trop. 2004 Sep;27(107):25-31.

Traditional oral health practices among Kanuri women of Borno State, Nigeria.

Bukar A, Danfillo IS, Adeleke OA, Ogunbodede EO.

Regional Centre for Oral Health Research and Training Initiatives for Africa,
Jos, Nigeria.

A structured questionnaire was administered on 495 women (urban 339, rural 156)
from two LGAs of Borno State, Nigeria, using the interviewer method. The age
range of the subjects was 12 to 80 years with a mean age (+/- SD) of 35.7 +/-
13.44 years. Majority (83.5%) did not have any formal education. Oral hygiene
tools used by the respondents included toothbrush/paste 36 (7.9%), chewing stick
250 (54.9%), charcoal 159 (34.9%) and ordinary water 10 (2.2%). Of those using
chewing sticks; 168 (67.2%) use Salvadora persica, 36 (14.4%) use Azadirachta
indica and 46 (18.4%) use Eucalyptus camaldulensis. Forty (8.1%) of the
respondents do not clean their teeth at all. Strong association was found
between choice of teeth cleaning material and educational level (P=0.000). Three
hundred and one (60.8%) of the respondents stain their teeth with flowers of
Solanum incanum or Nicotania tabacum while, 218 (44.0%) perform tattooing of lip
or gingivae and of this number 213 (97.7%) performed tattooing before marriage.
Tattooing is usually performed without local anaesthesia with thorns of
Balanites aegyptiaca and a mixture of charcoal & seeds of Acacia nilotica var.
tomentosa as pigments. It is concluded that traditional oral health practices
still constitute important part of the lifestyle in the study population.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15900821 [PubMed - indexed for MEDLINE]

77: Vet Parasitol. 2005 Jun 30;130(3-4):337-42.

Azadirachtin-impregnated traps for the control of Dermanyssus gallinae.

Lundh J, Wiktelius D, Chirico J.

Department of Parasitology, National Veterinary Institute and Swedish University
of Agricultural Sciences, SE-751 89 Uppsala, Sweden.

The effect of neem oil (azadirachtin), originating from the tree Azadirachta
indica, was investigated as a potential compound to control the poultry red
mite, Dermanyssus gallinae. In vitro tests were performed to determine the most
appropriate formulation of neem extracts and concentration of the substance to
be used. Cardboard traps containing 20% neem oil were placed at the mites'
aggregation sites, out of reach of the hens, in a floor system for layers
containing approximately 2400 birds. Treated traps were replaced every week for
4 weeks. Throughout the study, the parasite population was monitored by
collections of mites with untreated plastic traps. A 92% reduction of D.
gallinae was recorded.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15890446 [PubMed - indexed for MEDLINE]

78: J Ethnopharmacol. 2005 May 13;99(1):109-12.

Antioxidant activity of Siamese neem tree (VP1209).

Sithisarn P, Supabphol R, Gritsanapan W.

Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, 447
Sri-Ayuthaya Rd., Ratchatewi, Bangkok 10400, Thailand.

Leaves, fruits, flowers and stem bark extracts from the Siamese neem tree
(Azadirachta indica A. Juss var. siamensis Valeton, Meliaceae) were assessed for
antioxidant activity in vitro using the 1,1-diphenyl-2-picryl hydrazyl (DPPH)
scavenging assay, total antioxidant activity and inhibition of lipid
peroxidation in Chago K1 cancer cell culture by the thiobarbituric acid reactive
substances (TBARS) method. The results showed that leaf aqueous extract, flower
and stem bark ethanol extracts exhibited higher free radical scavenging effect
on the DPPH assay with 50% scavenging activity at 26.5, 27.9 and 30.6 microg/ml,
respectively. The total antioxidant activity of these extracts was found to be
0.959, 0.988 and 1.064 mM of standard trolox, respectively. At 100 microg/ml,
the flower ethanol and leaf aqueous extracts significantly decreased
malondialdehyde (MDA) levels (46.0 and 50.6%, respectively) by the TBARS method.
The results suggest that extracts from leaf, flower and stem bark of the Siamese
neem tree have strong antioxidant potential. This report supports the
ethnomedical use of young leaves and flowers of this plant as a vegetable bitter
tonic to promote good health.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15848028 [PubMed - indexed for MEDLINE]

79: Curr Med Chem Anticancer Agents. 2005 Mar;5(2):149-6.

Medicinal properties of neem leaves: a review.

Subapriya R, Nagini S.

Department of Biochemistry, Faculty of Science, Annamalai University,
Annamalainagar-608 002, Tamil Nadu, India.

Azadirachta indica, commonly known as neem, has attracted worldwide prominence
in recent years, owing to its wide range of medicinal properties. Neem has been
extensively used in Ayurveda, Unani and Homoeopathic medicine and has become a
cynosure of modern medicine. Neem elaborates a vast array of biologically active
compounds that are chemically diverse and structurally complex. More than 140
compounds have been isolated from different parts of neem. All parts of the neem
tree- leaves, flowers, seeds, fruits, roots and bark have been used
traditionally for the treatment of inflammation, infections, fever, skin
diseases and dental disorders. The medicinal utilities have been described
especially for neem leaf. Neem leaf and its constituents have been demonstrated
to exhibit immunomodulatory, anti-inflammatory, antihyperglycaemic, antiulcer,
antimalarial, antifungal, antibacterial, antiviral, antioxidant, antimutagenic
and anticarcinogenic properties. This review summarises the wide range of
pharmacological activities of neem leaf.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15777222 [PubMed - indexed for MEDLINE]

80: Environ Pollut. 2005 May;135(1):101-9.

Isoprene emission from tropical tree species.

Padhy PK, Varshney CK.

School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110
067, India. [email protected]

Foliar emission of isoprene was measured in nine commonly growing tree species
of Delhi, India. Dynamic flow enclosure technique was used and gas samples were
collected onto Tenax-GC/Carboseive cartridges, which were then attached to the
sample injection system in the gas chromatograph (GC). Eluting compounds were
analysed using a flame ionisation detector (FID). Out of the nine tree species,
isoprene emission was found in six species (Eucalyptus sp., Ficus benghalensis,
Ficus religiosa, Mangifera indica, Melia azedarach, and Syzygium jambolanum),
whereas, in the remaining three tree species (Alstonia scholaris, Azadirachta
indica, and Cassia fistula) no isoprene emission was detected or the levels of
emission were negligible or below the detection limit (BDL). Among six tree
species, the highest hourly emission (10.2 +/- 6.8 microg g(-1) leaf dry weight,
average of five seasons) was observed in Ficus religiosa, while minimum emission
was from Melia azedarach (2.2 +/- 4.9 microg g(-1) leaf dry weight, average of
five seasons). Isoprene emission (average of six species), over five seasons,
was found to vary between 3.9 and 8.5 microg g(-1) leaf dry weight during the
rainy season. In addition, significant diurnal variation in isoprene emission
was observed in each species. The preliminary estimate made in this study on the
annual biogenic VOC emission from India may probably be the first of its kind
from this part of the world.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15701397 [PubMed - indexed for MEDLINE]

81: Acta Crystallogr C. 2005 Feb;61(Pt 2):o70-2. Epub 2005 Jan 15.

The isomeric compounds nimbolide and isonimbolide.

Anand Solomon K, Malathi R, Rajan SS, Anitha G, Josepha Lourdu Raj J, Narasimhan
S, Suresh G, Gopalakrishnan G.

Department of Crystallography and Biophysics, University of Madras, Guindy
Campus, Chennai, India.

Nimbolide [systematic name:
acid gamma-lactone methyl ester], C27H30O7, was isolated from the leaves of
Azadirachta indica, and its isomer, isonimbolide [systematic name:
1-oxo-18,24-dinor-11,12-secochola-2,16,20,22-tetraene-4,11-dicarboxylic acid
gamma-lactone methyl ester], was prepared from a novel rearrangement reaction of
nimbolide, using boron trifluoride etherate and tetrabutylammonium bromide. The
reaction conditions are probably responsible for the ether cleavage, double-bond
rearrangement and reformation of the ether linkage. As a result, there are
conformational changes in two cyclopentane rings and the side-chain -CH2COOMe
group. In isonimbolide, an R(4)(4)(24) hydrogen-bond motif is observed.

PMID: 15699572 [PubMed - indexed for MEDLINE]

82: Life Sci. 2005 Feb 4;76(12):1325-38. Epub 2005 Jan 18.

Neuroprotective effect of Azadirachta indica on cerebral post-ischemic
reperfusion and hypoperfusion in rats.

Yanpallewar S, Rai S, Kumar M, Chauhan S, Acharya SB.

Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu
University, Varanasi, Uttar Pradesh 221 005, India.

We assessed the effect of Azadirachta indica (A. indica), a plant that has been
reported to possess antioxidant, anti-inflammatory and anxiolytic properties, on
cerebral reperfusion injury and long term cerebral hypoperfusion. When blood
flow to brain region that has undergone critical period of ischemia is
re-established, additional injury is to be expected from the reperfusion. In the
present study, bilateral common carotid artery (BCCA) occlusion for 30 min
followed by 45 min reperfusion resulted in increase in lipid peroxidation,
superoxide dismutase (SOD) activity and fall in total tissue sulfhydryl (T-SH)
groups. A. indica pretreatment (500 mg/kg/day x 7 days) attenuated the
reperfusion induced enhanced lipid peroxidation, SOD activity and prevented fall
in T-SH groups. Moreover, A.indica per se increased brain ascorbic acid level,
which was unchanged during reperfusion insult. Long-term cerebral hypoperfusion
induced by permanent BCCA occlusion has been reported to cause behavioral and
histopathological abnormalities. In the present study, as tested by open field
paradigm and Morris' water maze, a propensity towards anxiety and disturbances
of learning/memory were observed in animals subjected to hypoperfusion for 2
weeks. A. indica (500 mg/kg/day x 15 days) significantly reduced these
hypoperfusion induced functional disturbances. Reactive changes in brain
histology like gliosis, perivascular lymphocytic infiltration, recruitment of
macrophages and cellular edema following long term hypoperfusion were also
attenuated effectively by A. indica. We conclude that our study provides an
experimental evidence for possible neuroprotective potentiality of A. indica.

PMID: 15670613 [PubMed - indexed for MEDLINE]

83: Fitoterapia. 2005 Jan;76(1):54-61.

Antifilarial activity of Azadirachta indica on cattle filarial parasite Setaria

Mishra V, Parveen N, Singhal KC, Khan NU.

Natural Products Laboratory, Department of Chemistry, Aligarh Muslim University,
Aligarh- 202002, India.

Alcohol and aqueous extracts of flowers of Azadirachta indica were tested in
vitro for their potential antifilarial activity against whole worm, nerve muscle
(n.m.) preparation and microfilariae of Setaria cervi. The effects of alcohol
and aqueous extracts were similar in nature on the spontaneous movements of
whole worm and nerve muscle preparation. On the whole worm, the response was
characterized by initial increase in tone, rate and amplitude of contractions
followed by reversible paralysis. The initial stimulant effect is likely to be
due to irritant effect on the cuticle. Nerve muscle preparation responded to
both extracts by inhibition of spontaneous movements followed by reversible
paralysis; initial stimulation phase was absent. The inhibition was
concentration related. Alcohol and aqueous extracts had almost similar lethal
effect on the microfilariae of S. cervi, the LC50 being 15 and 18 ng/ml,

PMID: 15664463 [PubMed - indexed for MEDLINE]

84: Med Vet Entomol. 2004 Dec;18(4):449-52.

Toward development of neem-based repellents against the Scottish Highland biting
midge Culicoides impunctatus.

Blackwell A, Evans KA, Strang RH, Cole M.

Centre for Tropical Veterinary Medicine, Royal (Dick) School of Veterinary
Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin,
Midlothian, UK. [email protected]

Oil of neem, from the tree Azadirachta indica A. Juss (Meliaceae), was evaluated
for repellent and antifeedant activity against Culicoides biting midges
(Diptera: Ceratopogonidae), by three complementary methods with serial
dilutions. Electroantennograms revealed the sensitivity of Culicoides
nubeculosus (Meigen) females to neem > or = 0.10%. Culicoides impunctatus
Goetghebuer females were repelled by > or = 1% in a Y-tube olfactometer, Using a
membrane feeder for wild-caught parous females of C. impunctatus, the proportion
blood-feeding was significantly reduced by topical applications of neem oil > or
= 0.10% concentrations, with blood-feeding completely prevented by > or =1%. On
the basis of these response data, we developed 2% neem-based formulations for
personal protection against biting midges.

Publication Types:
Evaluation Studies

PMID: 15642014 [PubMed - indexed for MEDLINE]

85: J Biosci. 2004 Dec;29(4):409-16.

Bioefficacy and mode-of-action of some limonoids of salannin group from
Azadirachta indica A. Juss and their role in a multicomponent system against
lepidopteran larvae.

Koul O, Singh G, Singh R, Daniewski WM, Berlozecki S.

Insect Biopesticide Research Centre, 30 Parkash Nagar, Jalandhar 144 003, India.
[email protected]

Biological activities of the salannin type of limonoids isolated from
Azadirachta indica A. Juss were assessed using the gram pod borer Helicoverpa
armigera (Hubner) and the tobacco armyworm Spodoptera litura (Fabricius)
(Lepidoptera: Noctuidae). Inhibition of larval growth was concomitant with
reduced feeding by neonate and third instar larvae. All three compounds
exhibited strong antifeedant activity in a choice leaf disc bioassay with 2.0,
2.3 and 2.8 microg/cm(2) of 3-O-acetyl salannol, salannol and salannin,
respectively deterring feeding by 50% in S. litura larvae. In nutritional
assays, all three compounds reduced growth and consumption when fed to larvae
without any effect on efficiency of conversion of ingested food (ECI),
suggesting antifeedant activity alone. No toxicity was observed nor was there
any significant affect on nutritional indices following topical application,
further suggesting specific action as feeding deterrents. When relative growth
rates were plotted against relative consumption rates, growth efficiency of the
H. armigera fed diet containing 3-O-acetyl salannol, salannol or salannin did
not differ from that of starved control larvae (used as calibration curve),
further confirming the specific antifeedant action of salannin type of
limonoids. Where the three compounds were co-administered, no enhancement in
activity was observed. Non-azadirachtin limonoids having structural similarities
and explicitly similar modes of action, like feeding deterrence in the present
case, have no potentiating effect in any combination.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15625397 [PubMed - indexed for MEDLINE]

86: Pharmazie. 2004 Nov;59(11):876-8.

Hypoglycaemic effects of some plant extracts are possibly mediated through
inhibition in corticosteroid concentration.

Gholap S, Kar A.

School of Life Sciences, Devi Ahilya University, Indore, India.

To unravel the possible mechanism of glucose lowering activity, effects of ten
different plant extracts in the regulation of serum cortisol and glucose
concentrations were evaluated in male mice. While the extracts of Inula
racemosa, Boerhaavia diffusa and Ocimum sanctum decreased the serum
concentration of both cortisol and glucose, Aegle marmelos, Azadirachta indica
and Gymnema sylvestre extracts could exhibit hypoglycaemic activity without
altering the serum cortisol concentration. It appears that the hypoglycaemic
effects of former three plant extracts are mediated through their cortisol
inhibiting potency, whereas the mechanism for other plant extracts could be
different. Lipid-peroxidation was not enhanced by any of the plant extracts
(some were in fact, antiperoxidative in nature). As I. racemosa, B. diffusa and
O. sanctum exhibited antiperoxidative, hypoglycaemic and cortisol lowering
activities, it is suggested that these three plant extracts may potentially
regulate corticosteroid induced diabetes mellitus.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15587591 [PubMed - indexed for MEDLINE]

87: Indian J Exp Biol. 2004 Nov;42(11):1091-5.

Ultrastructural changes in cauda epididymidal epithelial cell types of
Azadirachta indica leaf treated rats.

Ghodesawar MG, Ahamed RN, Ahmed AW, Aladakatti RH.

Department of Post-Graduate Studies & Research in Zoology, Karnatak University,
Dharwad, India.

To assess if cauda epididymis is a target for the effect of A. indica leaves,
Wistar strain male albino rats were administered (po) A. indica leaves (100
mg/rat/day for 24 days). Transmission electron microscopic analysis revealed
that in the cauda epididymal epithelium the nuclei of principal cells were
enlarged and the number of coated micropinocytotic vesicles of the apical
cytoplasm decreased. Microvilli were missing and mitochondrial cristae and Golgi
complex were highly disrupted. The cytoplasm was abounding with lysosomal
bodies. The clear cells increased in perimeter and their nuclei increased in
size and contained lesser chromatin. The nuclear membrane bulged out. The
cytoplasm was vacuolized. Further, there was decrease in size of the lipid
droplets, mitochondria, Golgi complex, endoplasmic reticulum and there was
accumulation of lysosomal bodies. The changes in the principal and clear cells
appear to be due to the effect of the hypoandrogen status caused by treatment
with A. indica leaves and a direct action on the epididymal epithelium.

PMID: 15587115 [PubMed - indexed for MEDLINE]

88: J Submicrosc Cytol Pathol. 2004 Apr;36(2):149-54.

Effects of Azadirachta indica and Melia azedarach (Meliaceae) extracts from
leaves on Trypanosoma cruzi growth and ultrastructure.

Yanes A, Finol HJ, Hasegawa M.

Department of Cellular Biology, Simon Bolivar University, Caracas Venezuela.

The chloroformic extracts from dried fresh leaves ofAzadirachta indica A. Juss.
and Melia azedarach L. (Meliaceae) showed marked inhibitory activity on
epimastigotes growth of Trypanosoma cruzi, evidenced by 96-wells microtiter
plate bioassay and radioactive thymidine incorporation experiment. Each
chloroformic extract was separated using silica gel and alumina column. In
transmission electron microscopy the bioactive chromatographic fractions caused
ultrastructural changes in epimastigotes such as vacuolization probably induced
by degeneration of the kinetoplast-mitochondrion complex, organelle
degeneration, and cell division disruption. In spectral analysis these bioactive
fractions seemed to be composed mainly of fatty acid mixtures.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15554501 [PubMed - indexed for MEDLINE]

89: Toxicon. 2004 Dec 15;44(8):829-35.

Larvicidal action of ethanolic extracts from fruit endocarps of Melia azedarach
and Azadirachta indica against the dengue mosquito Aedes aegypti.

Wandscheer CB, Duque JE, da Silva MA, Fukuyama Y, Wohlke JL, Adelmann J, Fontana

Biomass Chemo/Biotechnology Laboratory (LQBB), Department of Pharmacy, Federal
University of Parana (UFPR), 80210-170 Curitiba, PR, Brazil.

Ethanolic extracts from the kernels of ripe fruits from the Indian Lilac Melia
azedarach and from the well-known Neem tree, Azadirachta indica were assayed
against larvae of Aedes aegypti, the mosquito vector of dengue fever. The
lethality bioassays were carried out according to the recommendations of the
World Health Organization. Extracts were tested at doses ranging from 0.0033 to
0.05 g% in an aqueous medium for 24 and 48 h, at 25 or 30 degrees C, with or
without feeding of the larvae. LC50, LC95 and LC99 were determined. Both seed
extracts proved lethal for third to fourth instar larvae. Non-fed A. aegypti
larvae were more susceptible to Azadirachta extracts at both temperatures. Under
a more realistic environmental situation, namely with fed larvae at 25 degrees
C, the death rates caused by the Melia extract were higher, although at 30
degrees C the extract of Azadirachta had an even higher lethality. Inter allia,
the LC50 values for the crude extracts of these two members of the Meliaceae
ranged from 0.017 to 0.034 g% while the LC99 values ranged from 0.133 to 0.189
g%. Since no downstream processing was undertaken to purify the active agents in
the extracts, our findings seem very promising, suggesting that it may be
possible to increase the larvicidal activity further by improving the extraction
and the fractionation of the crude limonoids, for instance removing the
co-extracted natural fats.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15530964 [PubMed - indexed for MEDLINE]

90: J Agric Food Chem. 2004 Nov 3;52(22):6824-9.

Effect of essential oils on the growth of Fusarium verticillioides and fumonisin
contamination in corn.

Fandohan P, Gbenou JD, Gnonlonfin B, Hell K, Marasas WF, Wingfield MJ.

Program on Agricultural and Food Technology, National Institute of Agricultural
Research of Benin, P.O. Box 128, Porto-Novo, Benin. [email protected]

Essential oils extracted by hydrodistillation from local plants in Benin,
western Africa, and oil from seeds of the neem tree (Azadirachta indica) were
evaluated in vitro and in vivo for their efficacy against Fusarium
verticillioides infection and fumonisin contamination. Fumonisin in corn was
quantified using a fluorometer and the Vicam method. Oils from Cymbopogon
citratus, Ocimum basilicum, and Ocimum gratissimum were the most effective in
vitro, completely inhibiting the growth of F. verticillioides at lower
concentrations over 21 days of incubation. These oils reduced the incidence of
F. verticillioides in corn and totally inhibited fungal growth at concentrations
of 8, 6.4, and 4.8 microL/g, respectively, over 21 days. At the concentration of
4.8 microL/g, these oils did not affect significantly fumonisin production.
However, a marked reduction of fumonisin level was observed in corn stored in
closed conditions. The oils adversely affected kernel germination at 4.8
microL/g and therefore cannot be recommended for controlling F. verticillioides
on stored corn used as seeds, when used at this concentration. The oil of neem
seeds showed no inhibitory effect but rather accelerated the growth of F.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15506822 [PubMed - indexed for MEDLINE]

91: Cell Biochem Funct. 2005 Jul-Aug;23(4):229-38.

Ethanolic leaf extract of neem (Azadirachta indica) inhibits buccal pouch
carcinogenesis in hamsters.

Subapriya R, Bhuvaneswari V, Ramesh V, Nagini S.

Department of Biochemistry, Faculty of Science, Annamalai University, Tamil
Nadu, India.

We evaluated the chemopreventive effects of ethanolic neem leaf extract in the
initiation and post-initiation phases of 7,12-dimethylbenz[a]anthracene
(DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. The frequency of bone
marrow micronuclei as well as the concentrations of lipid peroxides, ratio of
reduced to oxidized glutathione (GSH/GSSG), and the activities of the
GSH-dependent enzymes glutathione peroxidase (GPx) and glutathione-S-transferase
(GST) in the buccal pouch, liver and erythrocytes were used as biomarkers of
chemoprevention. All the hamsters painted with DMBA alone for 14 weeks developed
buccal pouch carcinomas that showed diminished lipid peroxidation and enhanced
antioxidant status associated with increased frequencies of bone marrow
micronuclei. In the liver and erythrocytes of tumour-bearing animals, enhanced
lipid peroxidation was accompanied by compromised antioxidant defences.
Administration of ethanolic neem leaf extract effectively suppressed
DMBA-induced HBP carcinogenesis as revealed by the absence of tumours in the
initiation phase and reduced tumour incidence in the post-initiation phase. In
addition, ethanolic neem leaf extract modulated lipid peroxidation and enhanced
antioxidant status in the pouch, liver and erythrocytes and reduced the
incidence of bone marrow micronuclei. The results of the present study,
demonstrate that ethanolic neem leaf extract inhibits the development of
DMBA-induced HBP tumours by protecting against oxidative stress. Copyright 2004
John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15473007 [PubMed - indexed for MEDLINE]

92: Med J Malaysia. 2004 May;59 Suppl B:208-9.

The effect of neem (Azadirachta indica) extract and dietary selenium on
distribution of selenium in hepatocarcinogenesis induced rat.

Hanachi P, Loh LN, Fauziah O, Rafiuz ZH, Tee ST, Lye CW, Lam TP.

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences,
Institute of Bioscience, Universiti Putra Malaysia 43400, Serdang.

Neem, Azadirachta indica, is a plant from the family Meliaceae, known as "Pokok
Semambu" in Malay community. It has been extensively used in India as
traditional Ayurvedic and folklore minedicine for the treatment of various
diseases. This study aimed to determine the distribution of selenium in the
liver of rats during hepatocarcinogenesis when neem aqueous extract and dietary
selenium was supplemented.

PMID: 15468891 [PubMed - indexed for MEDLINE]

93: Life Sci. 2004 Oct 29;75(24):2867-78.

Clinical studies on the effect of Neem (Azadirachta indica) bark extract on
gastric secretion and gastroduodenal ulcer.

Bandyopadhyay U, Biswas K, Sengupta A, Moitra P, Dutta P, Sarkar D, Debnath P,
Ganguly CK, Banerjee RK.

Department of Physiology, Indian Institute of Chemical Biology, 4, Raja S. C.
Mullick Road, Kolkata, 700032, India. [email protected]

We have shown earlier that Neem (Azadirachta indica) bark aqueous extract has
potent antisecretory and antiulcer effects in animal models and has no
significant adverse effect (Bandyopadhyay et al., Life Sciences, 71, 2845-2865,
2002). The objective of the present study was to investigate whether Neem bark
extract had similar antisecretory and antiulcer effects in human subjects. For
this purpose, a group of patients suffering from acid-related problems and
gastroduodenal ulcers were orally treated with the aqueous extract of Neem bark.
The lyophilised powder of the extract when administered for 10 days at the dose
of 30 mg twice daily caused a significant (p < 0.002) decrease (77%) in gastric
acid secretion. The volume of gastric secretion and its pepsin activity were
also inhibited by 63% and 50%, respectively. Some important blood parameters for
organ toxicity such as sugar, urea, creatinine, serum glutamate oxaloacetate
transaminase, serum glutamate pyruvate transaminase, albumin, globulin,
hemoglobin levels and erythrocyte sedimentation rate remained close to the
control values. The bark extract when taken at the dose of 30-60 mg twice daily
for 10 weeks almost completely healed the duodenal ulcers monitored by barium
meal X-ray or by endoscopy. One case of esophageal ulcer (gastroesophageal
reflux disease) and one case of gastric ulcer also healed completely when
treated at the dose of 30 mg twice daily for 6 weeks. The levels of various
blood parameters for organ toxicity after Neem treatment at the doses mentioned
above remained more or less close to the normal values suggesting no significant
adverse effects. Neem bark extract thus has therapeutic potential for
controlling gastric hypersecretion and gastroesophageal and gastroduodenal

Publication Types:
Clinical Trial
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 15454339 [PubMed - indexed for MEDLINE]

94: Ecotoxicol Environ Saf. 2004 Nov;59(3):332-9.

Biochemical effects of vepacide (from Azadirachta indica) on Wistar rats during
subchronic exposure.

Rahman MF, Siddiqui MK.

Biochemical Toxicology, Biology Division, Indian Institute of Chemical
Technology, Hyderabad 500 007, India. [email protected]

We investigated the effect of Vepacide (from Azadirachta indica), a neem-based
pesticide, on acid (AcP) and alkaline (AkP) phosphatase in different tissues of
male and female albino Wistar rats. Subchronic doses of Vepacide in coconut oil
(80, 160, and 320 mg/kg; maximum volume of 0.2 mL) were administered orally for
45 or 90 days. The administration of Vepacide resulted in a significant increase
in AcP and AkP in serum, kidney, lung, and liver tissue (AkP only in liver),
whereas a significant decrease of AcP in liver was observed in male and female
rats after 45 and 90 days of treatment with moderate and high doses. The
alterations in serum, liver, kidney, and lung tissues of both male and female
rats caused by this compound were statistically significant, and the changes
were also dose and time dependent. The alterations in male rats were not
statistically significant when compared with female rats, indicating that there
were no sexual differences. The withdrawal study (28 days post-treatment)
revealed significant recovery, indicating reversal of the toxic symptoms once
the toxicant was removed. There was a high degree of positive correlation
between results for serum as compared to those for kidney, lung, and liver (AkP
only for liver). However, there was a high negative correlation between AcP
results for serum as compared with those for liver. The alterations in these
enzymes indicated that lung tissue was the most susceptible, followed by liver
and kidney. AcP and AkP are marker enzymes, and their increase in serum, with
parallel increases in different tissues, might be due to the increased
permeability of plasma membranes. The decrease in liver AcP may be due to the
necrosis of cellular tissues. The changes observed in these enzyme activities
could be useful as biomarkers of exposure to Vepacide.

PMID: 15388273 [PubMed - indexed for MEDLINE]

95: J Med Food. 2004 Fall;7(3):334-9.

Effects of aqueous extracts of garlic (Allium sativum) and neem (Azadirachta
indica) leaf on hepatic and blood oxidant-antioxidant status during experimental
gastric carcinogenesis.

Arivazhagan S, Velmurugan B, Bhuvaneswari V, Nagini S.

Department of Biochemistry, Faculty of Science, Annamalai University,
Annamalainagar, Tamil Nadu, India.

The modifying effects of aqueous extracts of garlic and neem leaf during the
pre-initiation and post-initiation phases of gastric carcinogenesis induced by
N-methyl-N'-nitro-N-nitrosoguanidine were investigated in male Wistar rats. The
extent of lipid peroxidation and the status of phase II biotransformation
enzymes such as glutathione peroxidase and glutathione-S-transferase that use
reduced glutathione (GSH) as substrate were used to biomonitor the
chemopreventive potential of these extracts. Enhanced lipid peroxidation in the
liver and blood of tumor-bearing animals was accompanied by significant
decreases in the activities of GSH-dependent antioxidants in the pre-initiation
as well as in the post-initiation phases. Our results suggest that the
modulatory effects of garlic and neem leaf on hepatic and blood
oxidant-antioxidant status may play a key role in preventing cancer development
at extrahepatic sites.

PMID: 15383228 [PubMed - indexed for MEDLINE]

96: Phytochemistry. 2004 Aug;65(16):2363-7.

Tetracyclic triterpenoids from the leaves of Azadirachta indica.

Siddiqui BS, Afshan F, Gulzar T, Hanif M.

International Center for Chemical Sciences, H.E.J. Research Institute of
Chemistry, University of Karachi, Karachi, 75270, Pakistan.
[email protected]

Two new tetracyclic triterpenoids zafaral
dien-3,16-dione-21-al] (1) and meliacinanhydride
ha,12alpha-diacetoxy,1,14,20(22)-trien-3-one] (2) have been isolated from the
methanolic extract of neem leaves along with two known constituents nimocinol
and isomeldenin. Their structures and the relative configurations were
determined by spectroscopic methods ((1)H and (13)C NMR, IR, and MS) and 2D NMR

PMID: 15381008 [PubMed - indexed for MEDLINE]

97: Parasitology. 2004 Aug;129(Pt 2):245-53.

Evaluation of anthelmintic properties of some plants used as livestock dewormers
against Haemonchus contortus infections in sheep.

Githiori JB, Hoglund J, Waller PJ, Baker RL.

International Livestock Research Institute, Nairobi, Kenya. [email protected]

Gastrointestinal helminth infections remain a major constraint to livestock
production globally. This study evaluated anthelmintic efficacy of 7 plants used
as dewormers by farmers and pastoralists in Kenya. Thus 3 commercial
anthelmintics and 7 plant preparations were tested in lambs infected with 5000
or 3000 L3 Haemonchus contortus in 4 experiments. In the first experiment,
ivermectin, levamisole and albendazole were tested in 46 lambs. Seven plant
preparations of Hagenia abyssinica, Olea europaea var. africana, Annona
squamosa, Ananas comosus, Dodonea angustifolia, Hildebrandtia sepalosa and
Azadirachta indica were tested in 151 lambs in 3 experiments. All 3
anthelminitics were highly effective in reducing faecal egg counts (FEC) and
total worm counts (TWC) in lambs. Plant preparations had varying levels of crude
proteins from 2.6% for O. europaea to 18.4% for A. indica. Compared with
controls, no significant reductions in FEC were observed for any of the treated
groups either 2 or 3 weeks post-treatment. Lambs treated with A. squamosa and A.
comosus were slaughtered 4 weeks post-treatment. No significant differences were
observed in mean TWC or number of eggs per female worm between treated animals
and the controls. No significant improvements in weight gain were observed in
treated lambs.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15376783 [PubMed - indexed for MEDLINE]

98: J Hazard Mater. 2004 Sep 10;113(1-3):97-109.

Adsorption of Pb(II) from aqueous solution by Azadirachta indica (Neem) leaf

Bhattacharyya KG, Sharma A.

Department of Chemistry, Gauhati University, Guwahati 781014, Assam, India.
[email protected]

An adsorbent was developed from the mature leaves of the Neem (Azadirachta
indica) tree for removing Pb(II) from water. Adsorption was carried out in a
batch process with several different concentrations of Pb(II) by varying amount
of adsorbent, pH, agitation time and temperature. The uptake of the metal was
very fast initially, but gradually slowed down indicating penetration into the
interior of the adsorbent particles. Both first-order and second-order kinetics
were tested and it was found that the latter gave a better explanation. The
experimental data closely followed both Langmuir and Freundlich isotherms. The
adsorbent had a considerably high Langmuir monolayer capacity of 300 mg/g. A
small amount of the adsorbent (1.2 g/L) could remove as much as 93% of Pb(II) in
300 min from a solution of concentration 100mg/L at 300 K. The adsorption
continuously increased in the pH range of 2.0-7.0, beyond which the adsorption
could not be carried out due to the precipitation of the metal. The adsorption
was exothermic at ambient temperature and the computation of the parameters,
DeltaH, DeltaS and DeltaG, indicated the interactions to be thermodynamically

Publication Types:
Evaluation Studies

PMID: 15363519 [PubMed - indexed for MEDLINE]

99: Asia Pac J Clin Nutr. 2004;13(Suppl):S170.

The effect of Azadirachta indica on distribution of antioxidant elements and
glutathione S-transferase activity in the liver of rats during

Hanachi P, Fauziah O, Peng LT, Wei LC, Nam LL, Tian TS.

Department of Biomedical Science, Faculty of Medicine and Health Sciences,
Universiti Putra, Malaysia.

The liver is often the first organ to be infected by metastasizing cancer.
Hepatocarcinogenesis is one of the most prevalent and deadly cancers worldwide,
which ranks seventh among cancers in order of frequency of occurrence. Numbers
of natural and synthetic antioxidants are known to treat initiation and
promotion of chemical carcinogenesis in experimental animal models. The effect
of 5% w/v of Azadirachta indica extract in diethylnitrosamine and
acetylaminofluorene induced hepatocellular carcinoma, which is a vital mechanism
in cancer treatment, was studied in male Sprague dawly rats. The result of
microscopic observation of the lesion score during hepatocarcinogenesis revealed
that cells of cancer group without treatment were severely necrotic at week 12.
However, cells of cancer group with Azadirachta indica treatment appeared nearly
normal. The tracking of the elements during hepatocarcinogenesis was done using
energy filtering transmission electron microscope (EFTEM). According to EFTEM
results, some of antioxidant elements such Na, Ca, and P is highly distributed
in Azadirachta indica treated normal and cancer group. However, the distribution
is too low in normal control and cancer control group without Azadirachta indica
treatment. The obtained results have shown a significant, decrease (P=0.05) of
liver cytosol Glutathione S-transferase in cancer control group rats. Meanwhile,
treatment with Azadirachta indica caused overall increase in liver GST activity
nearly to control group. Distinct evidence from this study contribute that oral
administration of 5% Azadirachta indica extract demonstrated anticancer activity
by increasing the distribution of antioxidant elements and GST activity may to
protect cells in preneoplastic nodules in cancer treated groups. However, there
was no evidence of side effects of Azadirachta indica towards normal cells
indicating Azadirachta indica as a potential preventive agent for cancer.

PMID: 15294745 [PubMed - in process]

100: J Econ Entomol. 2004 Jun;97(3):1142-7.

Biological activity of volatile di-n-propyl disulfide from seeds of neem,
Azadirachta indica (Meliaceae), to two species of stored grain pests, Sitophilus
oryzae (L.) and Tribolium castaneum (Herbst).

Koul O.

Insect Biopesticide Research Centre, 30 Parkash Nagar, Model Town, Jalandhar,
144 003, India. [email protected]

Head space volatiles, including 73% di-n-propyl disulfide, were collected from
freshly crushed neem seeds. This compound along with previously reported diallyl
disulfide (di-2-propenyl disulfide) were toxic when applied topically or as a
fumigant to Tribolium castaneum adults and 8-, 12-, and 16-d-old larvae, and
Sitophilus oryzae adults. Di-n-propyl disulfide significantly decreased the
growth rate and dietary utilization with moderate inhibition of food consumption
in both insects. The total coefficient of deterrence for this compound ranged
between 68.5 and 178.6, which suggests that it has medium to very good deterrent
activity vis-a-vis the treatment concentration and instar. Di-n-propyl disulfide
and diallyl disulfide presented a similar effect on efficiency of conversion of
ingested food, which is reduced 3-fold; this implies that both compounds are
physiological toxicants. Present studies clearly demonstrate that di-n-propyl
disulfide could be a potent toxicant, fumigant, and feeding deterrent for stored
grain pests, if a suitable formulation and application procedure are developed.

PMID: 15279303 [PubMed - indexed for MEDLINE]

101: J Econ Entomol. 2004 Jun;97(3):916-23.

Behavioral and developmental effects of neem extracts on Clavigralla scutellaris
(Hemiptera: Heteroptera: Coreidae) and its egg parasitoid, Gryon fulviventre
(Hymenoptera: Scelionidae).

Mitchell PL, Gupta R, Singh AK, Kumar P.

Department of Zoology, University of Delhi, Delhi 110 007, India.
[email protected]

Extracts of neem, Azadirachta indica A. Juss, negatively affected feeding and
development of Clavigralla scutellaris (Westwood), a coreid pest of pigeonpea,
Cajanus cajan (L.) Millspaugh. Labial dabbing, pod wall penetration, and seed
damage by fifth instars were significantly reduced on beans, Phaseolus vulgaris
(L.), that had been dipped in aqueous, methanolic, or hexane extracts of neem
seed kernel. When fourth instars were dipped directly into aqueous extract,
developmental abnormalities of the wings occurred at all levels tested and
fecundity dropped to zero at concentrations above 0.3125%. The LC50 value was
3.14% (220 ppm azadirachtin) at 8 d. The scelionid wasp Gryon fulviventre
(Crawford) is an important natural enemy of Clavigralla spp.; egg mortality from
this parasitoid ranged from 37 to 85% during the fall cropping season. Feeding
by newly emerged wasps was dramatically reduced when honey was mixed with
aqueous neem suspension, but 6-d survivorship of adults did not differ
significantly from that of the control. Wasp oviposition behavior was altered
slightly when coreid eggs were treated with neem: the period of antennation was
significantly extended, but time for drilling, oviposition, and marking was
unaffected. Neem-dipped eggs were accepted for oviposition and progeny emerged
successfully from these treated eggs. Exposure of already parasitized eggs to
neem did not interfere with progeny emergence, longevity, or sex ratio. Thus,
neem extract and egg parasitoids seem to be compatible and promising control
strategies for C. scutellaris. Our results suggest that use of neem against
pod-sucking bugs will not interfere with natural control provided by G.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15279272 [PubMed - indexed for MEDLINE]

102: Indian J Exp Biol. 2003 Jun;41(6):636-40.

Lowering of blood sugar by water extract of Azadirachta indica and Abroma
augusta in diabetes rats.

Halim EM.

National Chemical Laboratory, Pune 411008, India. [email protected]

Combination (1:1 ) of water extract of dried powder of root and leaves (200
mg/kg body wt) of A. augusta and A. indica respectively was administered orally
to alloxan diabetic rats once a day for 8 weeks. This treatment caused
significant lowering of blood sugar in fasted as estimated by glucose tolerance
test. The treatment resulted in a significant reduction in serum lipids. Aqueous
extract also decreased the formation of lipid peroxides estimated as
thiobarbituric acid reactive substance, (TBARS), and increased antioxidants
(superoxide dismutase, catalase, glutathione peroxidase and glutathione
transferase) in erythrocytes. There was reduction in LPO as TBARS in heart,
liver, kidney, and muscles. It also prevented decrease in body weight. Present
study showed that Abroma augusta roots and A. indica leaves when given together
as water extract had hypoglycaemic action and had better effect than given

PMID: 15266913 [PubMed - indexed for MEDLINE]

103: Inflammopharmacology. 2004;12(2):153-76.

Mechanism of antiulcer effect of Neem (Azadirachta indica) leaf extract: effect
on H+-K+-ATPase, oxidative damage and apoptosis.

Chattopadhyay I, Nandi B, Chatterjee R, Biswas K, Bandyopadhyay U, Banerjee RK.

Department of Physiology, Indian Institute of Chemical Biology, 4 Raja S.C.
Mullick Road, Kolkata-700 032, India.

The mechanism of the antiulcer effect of Neem leaf aqueous extract to block
gastric lesions in rat has been studied with emphasis on acid secretion,
oxidative damage and apoptosis. The extract dose-dependently inhibits gastric
lesions induced by restraint-cold stress, indomethacin and ethanol. In stress
ulcer model, it is more effective than ranitidine but less effective than
omeprazole. It also dose-dependently blocks pylorus ligation and
mercaptomethylimidazole-induced acid secretion. In the pylorus-ligation model,
it is less effective than omeprazole but as effective as ranitidine. It inhibits
H+-K+-ATPase activity in vitro in concentration-dependent manner to inhibit acid
secretion. Oxidative membrane damage by hydroxyl radical (*OH) as measured by
lipid peroxidation in stress ulcer is significantly blocked by leaf extract.
Stress-induced apoptotic DNA fragmentation is also protected. The extract also
prevents *OH-mediated mucosal DNA damage in vitro by scavenging the *OH. Neem
leaf extract, thus, offers antiulcer activity by blocking acid secretion through
inhibition of H+-K+-ATPase and by preventing oxidative damage and apoptosis.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 15265317 [PubMed - indexed for MEDLINE]

104: J Ethnopharmacol. 2004 Sep;94(1):25-41.

Safety evaluation of neem (Azadirachta indica) derived pesticides.

Boeke SJ, Boersma MG, Alink GM, van Loon JJ, van Huis A, Dicke M, Rietjens IM.

Laboratory of Entomology, Wageningen University, P.O. Box 8031, 6700 EH, The

The neem tree, Azadirachta indica, provides many useful compounds that are used
as pesticides and could be applied to protect stored seeds against insects.
However in addition to possible beneficial health effects, such as blood sugar
lowering properties, anti-parasitic, anti-inflammatory, anti-ulcer and
hepatoprotective effects, also toxic effects are described. In this study we
present a review of the toxicological data from human and animal studies with
oral administration of different neem-based preparations. The non-aqueous
extracts appear to be the most toxic neem-based products, with an estimated safe
dose (ESD) of 0.002 and 12.5 microg/kg bw/day. Less toxic are the unprocessed
materials seed oil and the aqueous extracts (ESD 0.26 and 0.3 mg/kg bw/day, 2
microl/kg bw/day respectively). Most of the pure compounds show a relatively low
toxicity (ESD azadirachtin 15 mg/kg bw/day). For all preparations, reversible
effect on reproduction of both male and female mammals seem to be the most
important toxic effects upon sub-acute or chronic exposure. From the available
data, safety assessments for the various neem-derived preparations were made and
the outcomes are compared to the ingestion of residues on food treated with neem
preparations as insecticides. This leads to the conclusion that, if applied with
care, use of neem derived pesticides as an insecticide should not be

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15261960 [PubMed - indexed for MEDLINE]

105: Arch Environ Contam Toxicol. 2004 May;46(4):470-7.

Effect of herbal molluscicides and their combinations on the reproduction of the
snail Lymnaea acuminata.

Singh A, Singh DK.

Department of Zoology, DDU Gorakhpur University, India.

Effects of sublethal treatment (20 and 60% of LC50/24 h) of the plant-derived
molluscicides Annona squamosa Linn. and Lawsonia inermis Linn. and their
combinations with other herbal molluscicides, such as Cedrus deodara Roxb,
Azadirachta indica A. Juss, bulb powder of Allium sativum Linn. and Polianthes
tuberosa Linn., and oleoresin of Zingiber officinale Rosc., and acetogenins
extracted from the seeds of A. squamosa Linn., on the reproduction of the snail
Lymnaea acuminata have been studied. It was observed that the plant-derived
molluscicides singly and in binary combinations with other herbal molluscicides
and the extracted acetogenins caused a significant reduction in the fecundity,
hatchability, and survival of young snails. Withdrawal of the snails to fresh
water after the above treatment caused a significant recovery in the fecundity
of the snail Lymnaea acuminata. Twenty-four-hour sublethal treatment with the
acetogenins caused a maximum reduction in the protein, amino acid, DNA, and RNA
in the ovotestis of treated Lymnaea acuminata.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15253044 [PubMed - indexed for MEDLINE]

106: J Environ Sci Health A Tox Hazard Subst Environ Eng. 2004;39(6):1559-71.

Use of plants to monitor contamination of air by SO2 in and around refinery.

Abdul-Wahab SA, Yaghi B.

Mechanical and Industrial Engineering Department, Sultan Qaboos University,
Muscat, Sultanate of Oman. [email protected]

The generation of SO2 from a refinery may affect the surrounding environment.
Moreover, SO2 and its by-products are phytotoxic as berg. This study aims to
investigate plant responses to SO2. The work has been designed with emphasis on
using the plants directly in monitoring the contamination of the atmospheric air
by SO2. An assessment was made of the impacts of long-term SO2 emissions from an
oil refinery on plants located in nearby areas that are likely to be exposed to
emission fallout. Three different plant species (Prosopis cineraria. Azadirachta
indica, and Phoenix dactilifera) common to the environment of the Arabian Gulf
were selected at different distances and directions from the refinery. The
analysis of the sulphate contents of these plants were used as bioindicators for
monitoring SO2 concentration levels in and around the refinery. The results of
this study showed that the three different plant species responsed differently
to SO2 in terms of their sulphate contents. Generally, all three species were
found to be sensitive to SO2 exposure. Furthermore, the concentration of
sulphate was found to be much higher closer to the refinery. On the basis of
this study, it can be stated that even though SO2 levels were lower than the
permissible limit values, the sulphate contents accumulated in the plants were
likely to cause plant injury especially in the vicinity of the source. This
suggests that the present environmental guidelines for SO2 may not protect
sensitive plant species.

PMID: 15244337 [PubMed - indexed for MEDLINE]

107: Ann Agric Environ Med. 2004;11(1):45-52.

The occurrence and allergising potential of airborne pollen in West Bengal,

Boral D, Chatterjee S, Bhattacharya K.

Department of Botany, Visva-Bharati University, Santiniketan-731235, West
Bengal, India.

A continuous 2-year volumetric aerobiological survey was conducted in Berhampore
town, a centrally located and representative part of West Bengal, India. The aim
of the study was to assess the allergising potential of airborne pollen grains
of West Bengal. A total of 31 pollen types were identified of which Poaceae
(grasses) pollen showed maximum frequency, followed by Cyperaceae, Cassia sp.,
Acacia auriculiformis, etc. The seasonal periodicities of the pollen types and
their relationship to meteorological conditions were investigated. It was found
that the pollen concentration is positively correlated with temperature and
negatively correlated with rainfall and relative humidity. Clinical
investigations by skin prick test were carried out to detect allergenicity of
pollen types. Eighteen common airborne pollen types induced positive responses
of which pollen extracts of Saccharum officinarum (grass), Azadirachta indica,
Cocos nucifera, Phoenix sylvestris, Cyperus rotundus and Eucalyptus citriodora
showed strongest sensitising potential. This result is consistent with previous
investigations in different parts of West Bengal.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15236497 [PubMed - indexed for MEDLINE]

108: J Basic Clin Physiol Pharmacol. 2003;14(4):387-95.

Azadirachta indica adversely affects sperm parameters and fructose levels in vas
deferens fluid of albino rats.

Ghosesawar MG, Ahamed RN, Ahmed M, Aladakatti RH.

Post-Graduate Department of Zoology, Karnatak University, Dharwad 580 003,

Azadirachta indica treatment for 24 days in albino rats resulted in a decrease
in the total sperm count, sperm motility, and forward velocity in vas deferens
fluid. The percentage of abnormal sperm increased and the fructose content
decreased. As diminished levels of fructose parallel androgen deficiency, we
conclude that reduced androgen levels resulting from the anti-androgenic
property of A. indica leaves probably influences the physiological maturation of

Publication Types:
Comparative Study

PMID: 15198309 [PubMed - indexed for MEDLINE]

109: Chembiochem. 2004 Apr 2;5(4):408-21.

Neem--an omnipotent plant: a retrospection.

Brahmachari G.

Natural Product Laboratory, Department of Chemistry, Visva-Bharati University,
Santiniketan 731235, West Bengal, India. [email protected]

Neem (Azadirachta indica A. Juss.) has universally been accepted as a wonder
tree because of its diverse utility. Multidirectional therapeutic uses of neem
have been known in India since the Vedic times. Besides its therapeutic
efficacies, neem has already established its potential as a source of naturally
occurring insecticide, pesticide and agrochemicals. Safe and economically
cheaper uses of different parts of neem in the treatment of various diseases and
in agriculture are discussed in this article. It further deals with the active
chemical constituents of various neem formulations. Commercially available neem
products are also mentioned along with their respective applications.
Furthermore, evaluation of safety aspects of different parts of neem and neem
compounds along with commercial formulations are also taken into consideration.
Systematic scientific knowledge on neem reported so far is thus very useful for
the wider interests of the world community.

Publication Types:

PMID: 15185362 [PubMed - indexed for MEDLINE]

110: J Colloid Interface Sci. 2004 Jul 15;275(2):496-502.

Rapid synthesis of Au, Ag, and bimetallic Au core-Ag shell nanoparticles using
Neem (Azadirachta indica) leaf broth.

Shankar SS, Rai A, Ahmad A, Sastry M.

Materials Chemistry Division, National Chemical Laboratory, Pune-411 008, India.

We report on the use of Neem (Azadirachta indica) leaf broth in the
extracellular synthesis of pure metallic silver and gold nanoparticles and
bimetallic Au/Ag nanoparticles. On treatment of aqueous solutions of silver
nitrate and chloroauric acid with Neem leaf extract, the rapid formation of
stable silver and gold nanoparticles at high concentrations is observed to
occur. The silver and gold nanoparticles are polydisperse, with a large
percentage of gold particles exhibiting an interesting flat, platelike
morphology. Competitive reduction of Au3+ and Ag+ ions present simultaneously in
solution during exposure to Neem leaf extract leads to the synthesis of
bimetallic Au core-Ag shell nanoparticles in solution. Transmission electron
microscopy revealed that the silver nanoparticles are adsorbed onto the gold
nanoparticles, forming a core-shell structure. The rates of reduction of the
metal ions by Neem leaf extract are much faster than those observed by us in our
earlier studies using microorganisms such as fungi, highlighting the possibility
that nanoparticle biological synthesis methodologies will achieve rates of
synthesis comparable to those of chemical methods. Copyright 2004 Elsevier Inc.

PMID: 15178278 [PubMed]

111: Phytother Res. 2004 May;18(5):419-24.

Nimbidin suppresses functions of macrophages and neutrophils: relevance to its
antiinflammatory mechanisms.

Kaur G, Sarwar Alam M, Athar M.

Department of Medical Elementology and Toxicology, Faculty of Science, Jamia
Hamdard, Hamdard Nagar, New Delhi, India.

Nimbidin is a mixture of tetranortriterpenes and is the major active principle
of the seed oil of Azadirachta indica A. Juss (Meliaceae) possessing potent
antiinflammatory and antiarthritic activities. The present study revealed that
nimbidin significantly inhibited some of the functions of macrophages and
neutrophils relevant to the inflammatory response following both in vivo and in
vitro exposure. Oral administration of 5-25 mg/kg nimbidin to rats for 3
consecutive days significantly inhibited the migration of macrophages to their
peritoneal cavities in response to inflammatory stimuli and also inhibited
phagocytosis and phorbol-12-myristate-13-acetate (PMA) stimulated respiratory
burst in these cells. In vitro exposure of rat peritoneal macrophages to
nimbidin also inhibited phagocytosis and PMA stimulated respiratory burst in
these cells. Nimbidin also inhibited nitric oxide (NO) and prostaglandin E2
(PGE2) production in lipopolysaccharide (LPS) stimulated macrophages following
in vitro exposure, whereas interleukin 1 (IL-1) was only weakly inhibited.
Probing the mechanism of NO inhibition revealed that nimbidin ameliorated the
induction of inducible NO synthase (iNOS) without any inhibition in its
catalytic activity. In addition, nimbidin also attenuated degranulation in
neutrophils assessed in terms of release of beta-glucuronidase, myeloperoxidase
and lysozyme. The results suggest that nimbidin suppresses the functions of
macrophages and neutrophils relevant to inflammation. Thus nimbidin can be
valuable in treating inflammation/inflammatory diseases. Copyright 2004 John
Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15174005 [PubMed - indexed for MEDLINE]

112: J Environ Manage. 2004 Jul;71(3):217-29.

Azadirachta indica leaf powder as an effective biosorbent for dyes: a case study
with aqueous Congo Red solutions.

Bhattacharyya KG, Sharma A.

Department of Chemistry, Gauhati University, Guwahati 781014, Assam, India.
[email protected]

In the present work, the leaves of Azadirachta indica (locally known as the Neem
tree) in the form of a powder were investigated as a biosorbent of dyes taking
aqueous Congo Red solution as a model system. The sorbent was made from mature
Neem leaves and was investigated in a batch reactor under variable system
parameters such as concentration of the aqueous dye solution, agitation time,
adsorbent amount, pH, and temperature. An amount of 0.6 g of the Neem leaf
powder (NLP) per litre could remove 52.0-99.0% of the dye from an aqueous
solution of concentration 2.87 x 10(-2) mmol l(-1) with the agitation time
increasing from 60 to 300 min. The interactions were tested with respect to both
pseudo first-order and second-order reaction kinetics; the latter was found to
be more suitable. Considerable intra-particle diffusion was found to occur
simultaneously. The sorption process was in conformity with Langmuir and
Freundlich isotherms yielding values of the adsorption coefficients in the
following ranges: Freundlich n: 0.12-0.19, Kf: 0.1039-0.2648 L g(-1); Langmuir
qm: 41.24-128.26 g kg(-1), b: 443.3-1898.0 l mmol(-1), which supported
favourable adsorption. The Langmuir monolayer capacity (qm) was high and the
values of the coefficient b indicated the equilibrium, dye + NLP = dye...NLP
being shifted overwhelmingly towards adsorption. Thermodynamically, the sorption
process was exothermic with an average heat of adsorption of -12.75 kJ mol(-1).
The spontaneity of the sorption process was also confirmed by the favourable
values of Gibbs energy (mean values: -1.09 to -1.81 kJ mol(-1)) and entropy of
adsorption (range: -18.97 to -56.32 J mol(-1)K(-1)). The results point to the
effectiveness of the Neem leaf powder as a biosorbent for removing dyes like
Congo Red from water.

Publication Types:
Evaluation Studies

PMID: 15158285 [PubMed - indexed for MEDLINE]

113: Pest Manag Sci. 2004 May;60(5):459-64.

Comparison of anti-feedant and insecticidal activity of nimbin and salannin
photo-oxidation products with neem (Azadirachta indica) limonoids.

Simmonds MS, Jarvis AP, Johnson S, Jones GR, Morgan ED.

Royal Botanic Gardens, Kew, Richmond, Surrey, TW9 3AB, UK.

Photo-oxidation of the neem limonoids nimbin and salannin with UV light in the
presence of oxygen gives two isomeric lactone products per limonoid, nimbinolide
and isonimbinolide, and salanninolide and isosalanninolide, respectively. When
compared in insect tests with the important limonoids of neem seeds,
azadirachtin, nimbin and salannin, isonimbinolide and isosalanninolide show
activity greater than that of nimbin or salannin and in some respects show
activity approaching that of azadirachtin. The photo-oxidation products were
tested for anti-feedant activity and toxicity against larvae of three species of
Lepidoptera, Spodoptera littoralis (Boisd), Spodoptera frugiperda (FE Smith) and
Helicoverpa armigera (Hubner) and nymphs of the locusts Schistocerca gregaria
(Forskal) and Locusta migratoria (L).

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 15154512 [PubMed - indexed for MEDLINE]

114: J Ethnopharmacol. 2004 May;92(1):23-36.

Chemopreventive potential of Azadirachta indica (Neem) leaf extract in murine
carcinogenesis model systems.

Dasgupta T, Banerjee S, Yadava PK, Rao AR.

Cancer Biology and Applied Molecular Biology Laboratories, School of Life
Sciences, Jawaharlal Nehru University, New Delhi 110067, India.

Numerous laboratory studies reveal that various naturally occurring dietary
substances can modify the patho-physiological process of various metabolic
disorders and can be an effective preventive strategy for various diseases,
including cancer. Indian Neem tree, Azadirachta indica A. Juss. (family:
Meliaceae), contains at least 35 biologically active principles and is widely
grown all over the tropics. The effect of two different doses (250 and 500 mg
per kilogram body weight) of 80% ethanolic extract of the leaves of Azadirachta
indica were examined on drug metabolizing Phase-I and Phase-II enzymes,
antioxidant enzymes, glutathione content, lactate dehydrogenase, and lipid
peroxidation in the liver of 7-week-old Swiss albino mice. Also anticarcinogenic
potential of Azadirachta indica leaf extract was studied adopting protocol of
benzo(a)pyrene-induced fore-stomach and 7,12-dimethyl benz(a)anthracene
(DMBA)-induced skin papillomagenesis. Our primary findings reveal its potential
to induce only the Phase-II enzyme activity associated mainly with carcinogen
detoxification in liver of mice. The hepatic glutathione S-transferase (P <
0.005) and DT-diaphorase specific activities (P < 0.01) were elevated above
basal level. With reference to antioxidant enzymes the investigated doses were
effective in increasing the hepatic glutathione reductase (GR), glutathione
peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) activities
significantly (from P < 0.005 to P < 0.001). Reduced glutathione measured as
non-protein sulphydryl was found to be significantly elevated in liver (P <
0.005) and in extrahepatic organs (from P < 0.005 to P < 0.001) examined in our
study. Glutathione S-transferase (GST) and DT-diaphorase (DTD) showed a
dose-dependent increase in extrahepatic organs. Chemopreventive response was
measured by the average number of papillomas per mouse, as well as percentage of
tumor-bearing animals. There was a significant inhibition of tumor burden, in
both the tumor model system studied (from P < 0.005 to P < 0.001). Tumor
incidence was also reduced by both the doses of Azadirachta indica extract.
Copyright 2003 Elsevier Ireland Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15099843 [PubMed - indexed for MEDLINE]

115: Indian J Exp Biol. 2004 Apr;42(4):389-97.

Effect of Bacopa monniera and Azadirachta indica on gastric ulceration and
healing in experimental NIDDM rats.

Dorababu M, Prabha T, Priyambada S, Agrawal VK, Aryya NC, Goel RK.

Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu
University, Varanasi 221 005, India.

Gastric ulcers were induced in normal/NIDDM rats by various physical (2 hr cold
restraint stress and 4 hr pylorus ligation) and chemical agents (ethanol, 1
ml/200 g, oral, 1 hr before; aspirin, 200 mg/kg, oral, 4 hr) and duodenal ulcers
were induced by cysteamine (40 mg/200 g). Ulcer healing activity was studied in
gastric ulcers induced by acetic acid (50%) and HCI (0.6 M). The result
indicated that in both, normal and NIDDM rats, B. monniera extract (BME, 20-100
mg/kg) did not show any significant effect on blood glucose level, while A.
indica (AIE, 250-1000 mg/kg) significantly decreased it. However, both BME (50
mg/kg) and AIE (500 mg/kg) showed significant anti-ulcer and ulcer-healing
activities in normal and NIDDM rats. Further, the present results also indicated
that the ulcer protective effects of BME was more pronounced in non-diabetic,
while that of AIE was more in NIDDM rats. The anti-ulcer and ulcer-healing
activities of BME and AIE may be due to their effects on various mucosal
offensive and defensive factors, and correction of blood sugar level by AIE may
help to have more ulcer protective effect in NIDDM rats.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15088689 [PubMed - indexed for MEDLINE]

116: J Basic Microbiol. 2004;44(2):106-13.

Inhibition of patulin production by Penicillium expansum cultured with neem
(Azadirachta indica) leaf extracts.

Mossini SA, de Oliveira KP, Kemmelmeier C.

Department of Biochemistry, Universidade Estadual de Maringa, Maringa PR Brazil.

Aqueous extract of the leaves of neem [Azadirachta indica A. JUSS (Meliaceae)]
was tested in vitro for antifungal activity against Penicillium expansum.
Patulin production was inhibited during cultivation, when concentrations higher
than 50 mg/ml of neem leaf extract was added to the culture medium. Analyses of
mycotoxin production were performed by TLC and HPLC. Fungal growth and colony
characteristics, in the presence of the extract, were investigated and compared
with extract-free cultures. Copyright 2004 WILEY-VCH Verlag GmbH & Co. KGaA,

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15069669 [PubMed - indexed for MEDLINE]

117: Int Immunopharmacol. 2004 Mar;4(3):355-66.

Neem (Azadirachta indica) leaf mediated immune activation causes prophylactic
growth inhibition of murine Ehrlich carcinoma and B16 melanoma.

Baral R, Chattopadhyay U.

Department of Immunoregulation and Immunodiagnostics, Chittaranjan National
Cancer Institute, 37 S.P. Mookherjee Road, Kolkata 700026, India.
[email protected]

Conditional growth inhibition of murine Ehrlich carcinoma (EC) and B16 melanoma
(B16Mel) was observed, following treatment of mice (Swiss and C57BL/6) with
aqueous extract of neem (Azadirachta indica) (1 unit/mice/week for 4 weeks)
either before or after inoculation of 1 x 10(6) tumor cells. Tumor inoculation
after weekly injections for 4 weeks with neem leaf preparation (NLP) induced
significant reduction of tumor growth (both EC and B16Mel) and increased
survivability of mice. On the other hand, NLP treatment after tumor inoculation
demonstrated no tumor growth inhibition in the NLP treated group in comparison
to the PBS treated control. No direct cytotoxic effect of NLP towards EC and
B16Mel tumor cells was observed in vitro. The spleen cells of NLP treated mice
when mixed with inoculum of B16Mel tumor cells and injected into a group of
mice, tumor growth was found to be significantly reduced and survivability of
the tumor hosts increased remarkably in comparison to mice inoculated with tumor
along with normal spleen cells. Concanavalin A (ConA) induced proliferation of
lymphocytes from NLP treated mice was significantly higher than the lymphocytes
of untreated mice. In in vitro, NLP by itself had no proliferative effects on
lymphocytes but it co-stimulated ConA induced mitogenesis. NLP induced
lymphocytosis as evidenced by increased lymphocyte count in blood as well as
spleen. Flow cytometric evidence suggested that increase in CD4+ and CD8+ T
cells accounted for lymphocytosis. The conditional tumor growth retardation,
observed in mice treated with NLP before tumor inoculation, may be regulated by
NLP mediated immune activation, having prominent role in the cellular immune
function of the tumor host.

Publication Types:
Comparative Study

PMID: 15037213 [PubMed - indexed for MEDLINE]

118: Afr J Med Med Sci. 2003 Jun;32(2):159-65.

Implication of reproductive endocrine malfunction in male antifertility efficacy
of Azadirachta indica extract in rats.

Raji Y, Udoh US, Mewoyeka OO, Ononye FC, Bolarinwa AF.

Department of Physiology, College of Medicine, University of Ibadan, Ibadan,
Nigeria. [email protected]

The effects of the ethanol extract of Azadirachta indica stem bark on body and
organ weights, sperm morphology, counts and viability, serum levels of
testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH)
were studied in albino rats. Intraperitoneal administration (i.p) of the extract
for ten weeks caused significant dose-dependent decreases in weights of the
testis, epididymis and seminal vesicles but an increase in that of the adrenal
gland. Sperm counts, morphology and viability were adversely affected in the
extract treated rats. Rats that received 150 mgkg(-1) b.w. Azadirachta extract
were unable to impregnate female rats throughout the duration of the study.
However, these female rats conceived and sired physically normal litters about
four weeks after cohabitation with untreated male rats. Azadirachta indica
produced dose-dependent reduction in serum testosterone and LH but no change in
FSH levels. Most of the changes produced in this study were restored in recovery

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15032463 [PubMed - indexed for MEDLINE]

119: Z Naturforsch [C]. 2004 Jan-Feb;59(1-2):104-12.

Analysis of insecticidal Azadirachta indica A. Juss. fractions.

Siddiqui BS, Rasheed M, Ilyas F, Gulzar T, Tariq RM, Naqvi SN.

HEJ Research Institute of Chemistry, International Center for Chemical Sciences,
WHO Collaborating Centre, University of Karachi, Karachi-75270, Pakistan.
[email protected]

As a result of chemical investigation on the ethanolic extract of fresh fruit
coatings of Azadirachta indica A. Juss. (neem), twenty-seven compounds were
identified in non-polar to less polar fractions which showed pesticidal activity
determined by WHO method against Anopheles stephensi Liston. These
identifications were basically made through GC-EIMS and were further supported
by other spectroscopic techniques, including 13C NMR, UV and FTIR as well as
retention indices. Thus sixteen n-alkanes, 1-16; three aromatics
2,6-bis-(1,1-dimethylethyl)-4-methyl phenol (17), 2-(phenylmethylene)-octanal
(20), 1,2,4-trimethoxy-5-(1Z-propenyl)-benzene (27); three benzopyranoids
3,4-dihydro-4,4,5,8-tetramethylcoumarin (18),
3,4-dihydro-4,4,7,8-tetramethylcoumarin-6-ol (19),
1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta[g]-2-benzopyran (22);
one sesquiterpene methyl-3,7,11-trimethyl-2E,6E,10-dodecatrienoate (21); three
esters of fatty acids methyl 14-methyl-pentadecanoate (23), ethyl hexadecanoate
(24), ethyl 9Z-octadecenoate (25) and one monoterpene 3,7-dimethyl-1-octen-7-ol
(26) were identified. Except 6, 8, 24 and 25 all these compounds were identified
for the first time from the pericarp and fifteen of these, 1-3, 7, 9, 10, 17-23,
26, 27, are hitherto unreported previously from any part of the tree. Although
this tree is a rich source of various natural products, it is the first report
of identification of mono- and sesquiterpenes 26 and 21 and a potent
antioxidant, 17.

PMID: 15018062 [PubMed - indexed for MEDLINE]

120: J Ethnopharmacol. 2004 Feb;90(2-3):185-9.

Protective role of extracts of neem seeds in diabetes caused by streptozotocin
in rats.

Gupta S, Kataria M, Gupta PK, Murganandan S, Yashroy RC.

Division of Pharmacology and Toxicology, Indian Veterinary Research Institute,
Izatnagar 243 122, UP, India.

Effect of petroleum ether extracts of kernel (NSK) and husk (NSH) of neem
(Azadirachta indica A. Juss, Meliaceae) seeds on the prevention of oxidative
stress caused by streptozotocin (STZ) was investigated. Diabetes mellitus was
induced in adult male Wistar rats after administration of STZ (55 mg/kg b.wt.,
i.p., tail vein).The effect of NSK (2 gm/kg, b.wt.) and NSH (0.9 gm/kg, b.wt.)
orally for 28 days was investigated in diabetic rats. Insulin-treated diabetic
rats (6 U/kg, i.p., 28 days.) served as positive control. Diabetic rats given
normal saline served as diabetic control. Rats that neither received STZ nor
drugs served as normal control. Serum creatine phosphokinase (CPK) increased in
diabetic rats was significantly decreased on insulin, NSK, and NSH treatments.
The decrease in activities of superoxide dismutase (SOD) and catalase (CAT) and
increase in lipid peroxidation (LPO) of erythrocytes as observed in diabetes was
regained after insulin, NSH, and NSK treatments. However, there was
insignificant improvement in SOD, CAT, and LPO of kidney on NSK and NSH
treatment. In spite of increased CAT and SOD activities in liver and heart, LPO
was also increased in diabetic rats. Insulin, NSH, and NSK treatments
significantly protected animals from cardiac damage but not hepatic. Results
suggest that NSH and NSK prevent oxidative stress caused by STZ in heart and
erythrocytes. However, no such preventive effect was observed on renal and
hepatic toxicity.

PMID: 15013179 [PubMed - indexed for MEDLINE]

121: Plant Cell Rep. 2004 Jun;22(11):801-9. Epub 2004 Feb 25.

In vitro morphogenesis in zygotic embryo cultures of neem (Azadirachta indica A.

Chaturvedi R, Razdan MK, Bhojwani SS.

Department of Botany, University of Delhi, Delhi-7, India.
[email protected]

Immature zygotic embryo cultures of neem yielded highly regenerative cultures,
with the response varying with the embryo stage at culture. Early dicotyledonous
stage embryos were the most responsive followed by torpedo stage embryos. The
embryo cultures differentiated three types of regenerants: somatic embryos
(SEs), shoot buds and neomorphs. SEs exhibited morphological abnormalities such
as pluricotyledony, fusion of cotyledons and absence of cotyledons. Although
these SEs showed secondary embryogenesis, the occurrence of normal
dicotyledonous embryos was extremely rare. On MS basal medium 3% of SEs
developed a long tap root but a plumular shoot did not appear. However, it was
possible to regenerate plantlets from immature zygotic embryo cultures of neem
via neomorph formation and adventitious shoot bud formation. The transplantation
survival of these plants was more than 80%. Copyright 2004 Springer-Verlag

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 14986057 [PubMed - indexed for MEDLINE]

122: Pest Manag Sci. 2004 Feb;60(2):178-82.

Molluscicidal effects of neem (Azadirachta indica) extracts on edible tropical
land snails.

Ebenso IE.

Department of Animal Science, University of Uyo, PMB 1017, Uyo, Nigeria.
[email protected]

The effects of 350, 500 and 700 mg kg(-1) of crude extracts of neem, Azadirachta
indica A Juss, on edible tropical land snails Archachatina marginata and
Limicolaria aurora (Jay) were determined and compared with control using pawpaw,
Carica papaya L as bait. Responses were measured through normal feeding,
cessation of food intake, cessation of crawling, mucus secretion, lack of
response to mechanical stimuli (mortality) and decomposition. Results showed no
effects on the controls or snails exposed to neem seed oil extract. Crude
extracts of bark, root and leaf of neem at 500 and 700 mg kg(-1) produced
mortality after exposure for 48 h for L aurora and 72 h for A marginata.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 14971686 [PubMed - indexed for MEDLINE]

123: Acta Pharm. 2003 Dec;53(4):305-11.

Interaction between chloroquine sulphate and aqueous extract of Azadirachta
indica A. Juss (Meliaceae) in rabbits.

Nwafor SV, Akah PA, Okoli CO, Onyirioha AC, Nworu CS.

Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences,
University of Nigeria, Nsukka Enugu State, Nigeria. [email protected]

This study was carried out to investigate the effect of concurrent oral
administration of aqueous leaf extract of Azadirachta indica (Meliaceae) on the
pharmacokinetic properties of chloroquine sulphate in experimental rabbits. The
results indicated that concurrent administration of both agents resulted in a
significant decrease in serum concentration, slower absorption and elimination
as well as longer half-life of chloroquine sulphate. The highest relative
decrease of 78.0% was recorded 4 hours after concurrent administration, while
the smallest decrease (64.6%) occurred 24 hours after concurrent administration.
Significant reductions were also noted in some pharmacokinetic parameters of
chloroquine and included the area under the curve (71.9%), maximum serum
concentration (69.8%), absorption rate constant (37.3%), elimination rate
constant (53.9%), clearance rate (76.5%) and volume of distribution (47.2%).
However, there was a pronounced increase in the half-life of the drug (125.7%).

Publication Types:
Comparative Study

PMID: 14769237 [PubMed - indexed for MEDLINE]

124: Bioresour Technol. 2004 May;92(3):291-6.

Neem leaves as a source of fertilizer-cum-pesticide vermicompost.

Gajalakshmi S, Abbasi SA.

Centre for Pollution Control and Energy Technology, Pondicherry University,
Kalapet, Pondicherry 605-014, India.

Vermicomposting of neem (Azadirachta indica A. Juss) was accomplished in
"high-rate" reactors operated at the earthworm (Eudrilus eugeniae) densities of
62.5 and 75 animals per litre of reactor volume. Contrary to the fears that
neem--a powerful nematicide--might not be palatable to the annelids, the
earthworms fed voraciously on the neem compost, converting upto 7% of the feed
into vermicompost per day. Indeed the worms grew faster and reproduced more
rapidly in the neem-fed vermireactors than in the reactors fed with mango leaf
litter earlier studied by the authors (Gajalakshmi et al., 2003). Another set of
experiments on the growth, flowering, and fruition of brinjal (Solanum
melongena) plants with and without fertilization with vermicompost, revealed
that the vermicompost had a significantly beneficial impact.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 14766163 [PubMed - indexed for MEDLINE]

125: Vet Parasitol. 2003 Dec 30;118(3-4):215-26.

Evaluation of anthelmintic properties of extracts from some plants used as
livestock dewormers by pastoralist and smallholder farmers in Kenya against
Heligmosomoides polygyrus infections in mice.

Githiori JB, Hoglund J, Waller PJ, Leyden Baker R.

International Livestock Research Institute, P.O. Box 30709, Nairobi, Kenya.
[email protected]

Parasitic nematodes are among the most common and economically important
infectious diseases of grazing livestock, especially in small ruminants in the
tropics and subtropics in Kenya the control of gastrointestinal nematode
infections in sheep and goats is usually made with synthetic anthelmintics but
substantial levels of anthelmintic resistance have been recorded. A number of
medicinal plants, that may provide possible alternatives, and are used by
pastoralists and smallholder farmers in Kenya as deworming agents for their
livestock and equines, namely Aframomum sanguineum, Dodonea angustifolia,
Hildebrandtia sepalosa, Myrsine africana, Rapanea melanophloeos from Kenya, and
Azadirachta indica from Kenya and Malaysia, together with the chemicals embelin
and santonin that occur in some of these plants, were evaluated against
Heligmosomoides polygyrus in mice. Commercial anthelmintics, namely ivermectin,
pyrantel and piperazine, were also investigated, both to validate the mouse
model system and to assess efficacy of these drugs against H. polygyrus.
Pyrantel and ivermectin were highly effective in reducing the numbers of H.
polygyrus worms as well as eggs in faeces of the mice, but piperazine had a
lower activity. Application of santonin and M. africana significantly reduced
the number of total worm counts (TWC) but not faecal egg counts (FEC). The use
of embelin, R. melanophloeos and A. indica reduced FEC but not TWC. In all
cases, however, reductions were well below the a priori level of 70% required
for biological significance. A. sanguineum, D. angustifolia and H. sepalosa had
no effect on either TWC or FEC. In conclusion, none of the plant preparations
had any biologically significant anthelmintic effect in this monogastric
host-parasite model system.

Publication Types:
Evaluation Studies
Research Support, Non-U.S. Gov't

PMID: 14729169 [PubMed - indexed for MEDLINE]

126: J Ethnopharmacol. 2004 Jan;90(1):167-70.

Effects of Azadirachta indica extract on gastric ulceration and acid secretion
in rats.

Raji Y, Ogunwande IA, Osadebe CA, John G.

Department of Physiology, College of Medicine, University of Ibadan, Ibadan,
Nigeria. [email protected]

The effect of Azadirachta indica extract on gastric ulceration was studied in
albino rats. Azadirachta indica extract (100-800 mg/kg p.o., 100-25 mg/kg i.p.)
significantly inhibited gastric ulceration induced by indomethacin (40 mg/kg).
Administration of 800 mg/kg p.o. and 250 mg/kg i.p. caused 100% cytoprotection
against indomethacin (40mg/kg, i.p.)-induced gastric ulceration. This action was
accompanied by a dose-dependent decrease in total gastric acidity. In order to
investigate the probable mechanism of Azadirachta indica antiulcer activity, the
effect of the extract alone and in combination with histamine (1mg/kg) and
cimetidine (0.12 mg/kg) on gastric acid secretion in situ was studied.
Azadirachta indica (250 mg/kg) significantly inhibited the basal and
histamine-induced gastric acid secretion. Cimetidine seemed to augment
Azadirachta indica inhibition of gastric acid secretion.The results suggest that
the stem bark extract of Azadirachta indica possesses antiulcer agents, which
probably act via histamine H(2) receptor.

PMID: 14698526 [PubMed - indexed for MEDLINE]

127: J Ethnopharmacol. 2004 Jan;90(1):99-103.

Evaluation of antiplaque activity of Azadirachta indica leaf extract gel--a
6-week clinical study.

Pai MR, Acharya LD, Udupa N.

Department of Pharmaceutics, College of Pharmaceutical Sciences, Manipal Academy
of Higher Education, 576119, Manipal, India

Various chemical agents have been evaluated over the years with respect to their
antimicrobial effects in the oral cavity; however, all are associated with side
effects that prohibit regular long-term use. Therefore, the effectiveness of
neem (Azadirachta indica A. Juss) leaf extract against plaque formation was
assessed in males between the age group of 20-30 years over a period of 6 weeks.
Present study includes formulation of mucoadhesive dental gel containing
Azadirachta indica leaf extract (25 mg/g). A 6-week clinical study was conducted
to evaluate the efficacy of neem extract dental gel with commercially available
chlorhexidine gluconate (0.2% w/v) mouthwash as positive control. Microbial
evaluation of Streptococcus mutans and Lactobacilli species was carried out to
determine the total decrease in the salivary bacterial count over a period of
treatment using a semi-quantitative four quadrant streaking method. The results
of the study suggested that the dental gel containing neem extract has
significantly (P<0.05) reduced the plaque index and bacterial count than that of
the control group.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 14698516 [PubMed - indexed for MEDLINE]

128: Pest Manag Sci. 2003 Nov;59(11):1250-4.

Acaricidal effects of cardiac glycosides, azadirachtin and neem oil against the
camel tick, Hyalomma dromedarii (Acari: Ixodidae).

Al-Rajhy DH, Alahmed AM, Hussein HI, Kheir SM.

Department of Plant Protection, College of Agriculture, King Saud University, PO
Box 2460, Riyadh 11451, Saudi Arabia.

The cardiac glycoside, digitoxin, from Digitalis purpurea L (Scrophulariaceae),
a cardiac glycosidal (cardenolide) extract from Calotropis procera (Ait) R Br
(Asclepiadaceae), azadirachtin and neem oil from Azadirachta indica A Juss
(Meliaceae) were tested for their effects against larvae and adult stages of the
camel tick, Hyalomma dromedarii Koch (Acari: Ixodidae). The contact LC50 values
of the first three materials against adults were 4.08, 9.63 and >40.7 microg
cm(-2), respectively, whereas the dipping LC50 values of the four materials were
409.9, 1096, >5000 and >5000 mg litre(-1), respectively. Contact and dipping
LC50 values of the extract and azadirachtin against larvae were 6.16, >20.3
microg cm(-2) and 587.7 and >2500 mg litre(-1), respectively. Azadirachtin had
no effects on egg production or feeding of adults up to 5000 mg litre(-1);
however at 2500 mg litre(-1), it caused significant reduction in feeding
activity of larve, prolonged the period for moulting to nymphal stage, and
caused 60% reduction in moultability. Results of the two cardiac glycoside
materials are comparable with those of several commercial acaricides. The risks
and benefits associated with the use of cardiac glycosides are considered.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 14620053 [PubMed - indexed for MEDLINE]

129: J Ethnopharmacol. 2003 Dec;89(2-3):217-9.

Possible mechanism of hepatoprotective activity of Azadirachta indica leaf
extract: part II.

Chattopadhyay RR.

Biometry Research Unit, Indian Statistical Institute, 203, Barrackpore Trunk
Road, Kolkata 700 108, India. [email protected]

Hepatoprotective activity of Azadirachta indica leaf extract against paracetamol
induced hepatic damage in rats has already been reported. In the present
investigation effects of Azadirachta indica leaf extract on blood and liver
glutathione, Na+K(+)-ATPase activity and thiobarbutiric acid reactive substances
against paracetamol induced hepatic damage in rats have been studied with a view
to elucidate possible mechanism behind its hepatoprotective action. It was
interesting to observe that Azadirachta indica leaf extract has reversal effects
on the levels of above mentioned parameters in paracetamol hepatotoxicity.
Possible mechanism behind the results are discussed.

PMID: 14611885 [PubMed - indexed for MEDLINE]

130: Vet Parasitol. 2003 Nov 3;117(1-2):51-60.

The anthelmintic efficacy of five plant products against gastrointestinal
trichostrongylids in artificially infected lambs.

Hordegen P, Hertzberg H, Heilmann J, Langhans W, Maurer V.

Department of Veterinary Parasitology, Research Institute of Organic
Agriculture, Ackerstrasse, CH-5070 Frick, Switzerland.

Forty-eight helminth-free lambs were divided into eight groups (A-H) of six
animals. Groups A-G were infected artificially with 10,000 third stage larvae of
Haemonchus contortus and 20,000 third stage larvae of Trichostrongylus
colubriformis, whereas group H remained uninfected. Thirty days post-infection
the lambs were treated orally with a single dosage of one of the following
products: group A with 3 mg/kg body weight (BW) of an aqueous ethanol extract
(70%, v/v) of the seeds of Azadirachta indica A. Juss syn. Melia azedarach L.
(Meliaceae); group B with 1 g/kg BW of a raw powder of the leaves of Ananas
comosus (L.) Merr. (Bromeliaceae); group C with 0.3 mg/kg BW of an aqueous
ethanol extract of a 1:1 mixture (g/g) of Vernonia anthelmintica (L.) Willd.
(Asteraceae) seeds and Embelia ribes Burm (Myrsinaceae) fruits; group D with 183
mg/kg BW of an aqueous ethanol extract of the whole plants of Fumaria parviflora
Lam. (Fumariaceae); group E with 28 mg/kg BW of an aqueous ethanol extract of
the seeds of Caesalpinia crista L. (Caesalpiniaceae); group F with 25 mg/kg BW
of pyrantel tartrate and group G with 50% ethanol. Group H remained untreated.
Only the ethanol extract of F. parviflora caused a strong reduction of the
faecal egg counts (100%) and a 78.2 and 88.8% reduction of adult H. contortus
and T. colubriformis on day 13 post-treatment. The extract was as effective as
the reference compound pyrantel tartrate. Therefore, the ethanol extract itself
or single constituents of F. parviflora could be a promising alternative source
of anthelmintic for the treatment of gastrointestinal trichostrongylids in small

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 14597279 [PubMed - indexed for MEDLINE]

131: Bioorg Med Chem Lett. 2003 Nov 17;13(22):4111-5.

Biological investigation and structure-activity relationship studies on
azadirone from Azadirachta indica A. Juss.

Nanduri S, Thunuguntla SS, Nyavanandi VK, Kasu S, Kumar PM, Ram PS, Rajagopal S,
Kumar RA, Deevi DS, Rajagopalan R, Venkateswarlu A.

Discovery Chemistry, Dr. Reddy's Laboratories Ltd., Discovery Research, Bollaram
Road, Miyapur, Hyderabad 500 050, India. [email protected]

Azadirone 1, a limonoidal constituent of Azadirachta indica is found to possess
potent cytotoxic activity against a panel of human cancer cell lines in our in
vitro studies. In vitro screening of a number of semi-synthetic analogues of 1
revealed that the alpha,beta-unsaturated enone moiety or its equivalent
conjugated system in A-ring, C-7 acetyloxy/chloroacetyloxy or keto group in
B-ring and the furan moiety are responsible for the activity of 1 and its
analogues. Compound 1 and two of the semi-synthetic analogues 10 and 13 were
found to possess good in vivo antitumor activity in modified hollow fiber animal

PMID: 14592518 [PubMed - indexed for MEDLINE]

132: Contraception. 2003 Sep;68(3):225-9.

Spermicidal activity of Azadirachta indica (neem) leaf extract.

Khillare B, Shrivastav TG.

Department of Reproductive Biomedicine, National Institute of Health and Family
Welfare, Munirka, New Delhi, India-110067. [email protected]

The present study was carried out to evaluate the effective concentration of
aqueous extract of old and tender Azadirachta indica (neem) leaves to immobilize
and kill 100% human spermatozoa within 20 s. Sander-Cramer test was used to
study the spermicidal activity of neem leaf extract. Under the test conditions,
minimum effective spermicidal concentrations for tender and old leaf extracts
were 2.91 +/- 0.669 mg/million sperm and 2.75 +/- 0.754 mg/million sperm,
respectively. The effect of extracts on morphology and viability of sperm was
also studied and no change was observed in morphology of head, mid-piece and
tail and no viable sperm seen. The leaf extracts were found to be water soluble
and carbohydrate in nature. The effect of different concentrations of extracts
(old and tender) on percentage motility of the sperm was also studied. With an
increase in concentration, there is a linear decrease in percentage motility,
becoming zero at a 3-mg dose within 20 s.

PMID: 14561544 [PubMed - indexed for MEDLINE]

133: J Agric Food Chem. 2003 Oct 22;51(22):6456-60.

Prenylated flavanones isolated from flowers of Azadirachta indica (the neem
tree) as antimutagenic constituents against heterocyclic amines.

Nakahara K, Roy MK, Ono H, Maeda I, Ohnishi-Kameyama M, Yoshida M,
Trakoontivakorn G.

Japan International Research Center for Agricultural Sciences (JIRCAS), 1-1
Owashi, Tsukuba, Ibaraki 305-8686, Japan. [email protected]

Four prenylated flavanones were isolated from the methanol extract of the
flowers of Azadirachta indica (the neem tree) as potent antimutagens against
Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole) in the Salmonella
typhimurium TA98 assay by activity-guided fractionation. Spectroscopic
properties revealed that those compounds were
5,7,4'-trihydroxy-8-prenylflavanone (1),
5,4'-dihydroxy-7-methoxy-8-prenylflavanone (2),
5,7,4'-trihydroxy-3',8-diprenylflavanone (3), and
5,7,4'-trihydroxy-3',5'-diprenylflavanone (4). All isolated compounds were found
for the first time in this plant. The antimutagenic IC(50) values of compounds
1-4 were 2.7 +/- 0.1, 3.7 +/- 0.1, 11.1 +/- 0.1, and 18.6 +/- 0.1 microM in the
preincubation mixture, respectively. These compounds also similarly inhibited
the mutagenicity of Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole) and PhIP
(2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine). All of the compounds 1-4
strongly inhibited ethoxyresorufin O-dealkylation activity of cytochrome P450 1A
isoforms, which catalyze N-hydroxylation of heterocyclic amines. However,
compounds 1-4 did not show significant inhibition against the direct-acting
mutagen NaN(3). Thus, the antimutagenic effect of compounds 1-4 would be mainly
based on the inhibition of the enzymatic activation of heterocyclic amines.

PMID: 14558762 [PubMed - indexed for MEDLINE]

134: Arch Insect Biochem Physiol. 2003 Oct;54(2):68-76.

Erratum in:
Arch Insect Biochem Physiol. 2004 Jan;55(1):49.

A continuous spectrophotometric assay for the determination of diamondback moth
esterase activity.

He X.

Beneficial Insects Research Unit, KSARC, Agricultural Research Service, U. S.
Department of Agriculture, Weslaco, Texas 78596, USA. [email protected]

Conventional methods to determine esterase activity from insects are composed of
a three-step process where the enzyme is allowed to hydrolyze a 1-naphthyl
acetate substrate, that reaction is quenched by a SDS detergent, and then a Fast
Blue B dye complex is formed with 1-naphthol, the product of 1-naphthyl acetate
hydrolysis. These methods measure dye-product complex rather than the product,
1-naphthol. A new assay is presented that continuously monitors the formation of
1-naphthol with the hydrolysis of an esterase substrate. The esterase activity
was determined as the slope of the linear regression change in absorbance over
time at 320 nm. The continuous assay provides a simple, rapid, and sensitive
method for measuring esterases extracted from a single diamondback moth in 1-10
min. The detection limit of the assay is approximately 0.6 microM 1-naphthol.
The 1-naphthol product from the esterase reaction was confirmed by HPLC
analysis. According to the assay, the K(m) and V(max) values of the esterase
were 28 +/- 2 microM and 6.0 +/- 0.1 microM/min, respectively, at 37 degrees C
for 1-naphthyl acetate. The K(i) value was 9 +/- 2 microM using azadirachtin, an
insecticide from neem tree, Azadirachta indica (A.Juss). Azadirachtin was a
reversible competitive inhibitor of the esterase activity.

PMID: 14518005 [PubMed - indexed for MEDLINE]

135: Phytother Res. 2003 Aug;17(7):807-10.

Evaluation of the antimalarial properties and standardization of tablets of
Azadirachta indica (Meliaceae) in mice.

Isah AB, Ibrahim YK, Iwalewa EO.

Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of
Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria.

The antimalarial activities of the tablet suspension of the bark and leaf of
Azadirachta indica were evaluated on Plasmodium yoelli nigeriensis infected
mice. The tablet suspensions exhibited high prophylactic, mode-rate suppressive
and a very minimal curative schizonticidal effect. No animal was cured of the
infection in the curative test and there was not much increase in the survival
time of the animals compared with the control. The tablet suspensions from the
leaf and bark at a concentration of 800 mg/kg and chloroquine at a concentration
of 62.5 mg/kg body weight produced average percentage (%) parasitaemia of 79.6%,
68.2% and 99.5% for leaf, bark and chloroquine, respectively, in
chemosuppression. Also in the prophylactic treatment, the tablet suspensions at
800 mg/kg and pyrimethamine at a concentration of 0.35 mg/kg gave an average
parasitaemia reduction of 75.3%, 65.6% and 98.3% for the leaf, bark and
pyrimethamine, respectively. There was a clear indication that both tablet
suspensions from the leaf and bark possess antimalarial activity and a
suspension from the former is relatively more effective than the bark.
Extrapolation of the results from the antimalarial activity of the tablet
suspension of the crude plant parts showed that an adult human would need to
ingest a minimum of 48 g of the powdered plant material per day, an amount that
is impracticable. A survival index value of 0.33 was obtained with the 800 mg/kg
dose level, indicating that the tablet suspension has some moderate beneficial
effect. Copyright 2003 John Wiley & Sons, Ltd.

PMID: 12916083 [PubMed - indexed for MEDLINE]

136: Pharmazie. 2003 Jul;58(7):512-7.

Chemoprotective effects of ethanolic extract of neem leaf against MNNG-induced
oxidative stress.

Subapriya R, Kumaraguruparan R, Chandramohan KV, Nagini S.

Department of Biochemistry, Faculty of Science, Annamalai University,
Annamalainagar, Tamil Nadu, India.

We evaluated the modifying effects of ethanolic extract of neem leaves
(Azadirachta indica A. Juss) on oxidative stress induced by the potent gastric
carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in male Wistar rats. The
extent of lipid peroxidation and the status of the antioxidants superoxide
dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione
peroxidase (GPx) and glutathione S-transferase (GST) were used as intermediate
endpoints of chemoprevention. Three different concentrations of ethanolic neem
leaf extract (100, 200 and 400 mg kg(-1) body weight) were administered by
intragastric intubation (i.g) for five consecutive days followed by MNNG (i.g)
1.5 h after the final administration. Enhanced lipid peroxidation was
accompanied by compromised antioxidant defences in the stomach, liver and
erythrocytes of MNNG-treated rats. Pretreatment with ethanolic neem leaf extract
at a dose of 200 mg/kg body weight (bw) significantly lowered the concentration
of lipid peroxides and increased antioxidant levels. Our results demonstrate
that neem leaf exerts its chemoprotective effects on MNNG- induced oxidative
stress by decreasing lipid peroxidation and enhancing the antioxidant status.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12889539 [PubMed - indexed for MEDLINE]

137: Phytomedicine. 2003;10(5):391-6.

Effect of Azadirachta indica on paracetamol-induced hepatic damage in albino

Yanpallewar SU, Sen S, Tapas S, Kumar M, Raju SS, Acharya SB.

Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu
University, Varanasi, India.

Azadirachta indica, a plant used widely in Ayurveda, has been reported to have
anti-inflammatory, immunomodulatory and adaptogenic properties. The present
study evaluates its hepatoprotective role. Fresh juice of tender leaves of
Azadirachta indica (200 mg/kg body wt. p.o.) inhibited paracetamol (2 g/kg body
wt. p.o.)-induced lipid peroxidation and prevented depletion of sulfhydryl
groups in liver cells. There was an increase in serum marker enzymes of hepatic
damage (aspartate transaminase, alanine transaminase and alkaline phosphatase)
after paracetamol administration. Azadirachta indica pretreatment stabilized the
serum levels of these enzymes. Histopathological observations of liver tissues
corroborated these findings.

PMID: 12834004 [PubMed - indexed for MEDLINE]

138: J Agric Food Chem. 2003 Jul 2;51(14):3966-72.

An efficient method for the purification and characterization of nematicidal
azadirachtins A, B, and H, using MPLC and ESIMS.

Sharma V, Walia S, Kumar J, Nair MG, Parmar BS.

Division of Agricultural Chemicals, Indian Agricultural Research Institute, New
Delhi-110 012, India.

Azadirachtin A enriched concentrate containing 60% active ingredient (a.i.) was
prepared from the methanolic extract of the de-fatted neem (Azadirachta indica
A. Juss) seed kernels. Azadirachtins A, B, and H, the three major bioactive
constituents of neem seed kernel, were purified from this methanolic concentrate
by employing reverse phase medium-pressure liquid chromatography (MPLC), using
methanol-water solvent system as an eluant. The three pure azadirachtin
congeners thus obtained were characterized by their unique mass spectral
fragmentation, using electrospray probe in positive ion mode (ESI). All three
azadirachtins exhibited nematicidal and antifungal activities. Azadirachtin B
was the most effective against the reniform nematode Rotylenchulus reniformis
(EC(50) 96.6 ppm), followed by Azadirachtin A (119.1 ppm) and H (141.2 ppm). At
200-ppm concentration, the test compounds caused 50-65% mortality of
Caenorhabditis elegans nematode. Azadirachtin H showed the highest activity
against the phytophagous fungi Rhizoctonia solani (EC(50) 63.7 ppm) and
Sclerotium rolfsii (EC(50) 43.9 ppm), followed by B and A. The isolation of pure
azadirachtins A, B, and H directly by MPLC purification from its concentrate and
their characterization by ESIMS are unique and less time-consuming.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12822931 [PubMed - indexed for MEDLINE]

139: J Plant Physiol. 2003 May;160(5):557-64.

An efficient protocol for the production of triploid plants from endosperm
callus of neem, Azadirachta indica A. Juss.

Chaturvedi R, Razdan MK, Bhojwani SS.

Department of Botany, Department of Plant Molecular Biology, University of Delhi
South Campus, Benito Juarez Road, Dhaula Kuan, New Delhi-110021, India.
[email protected]

Triploid plants of neem were obtained by immature endosperm culture. Immature
seeds, at the early dicotyledonous stage of embryo development, is the best
explant to raise endosperm callus on MS + NAA (5 mumol/L) + BAP (2 mumol/L) + CH
(500 mg L-1). Maximum shoot bud differentiation from the endosperm callus
occurred on MS + 5 mumol/L BAP. Shoots were multiplied by forced axillary
branching and rooted in vitro. The plants were established in soil. Over 66% of
the plants were triploid with chromosome number 2n = 3x = 36. A characteristic
feature of the shoots of endosperm origin is the presence of a large number of
multi-cellular glands.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12806785 [PubMed - indexed for MEDLINE]

140: Plant Cell Rep. 2003 Feb;21(6):531-7. Epub 2002 Dec 20.

Production of haploids of neem (Azadirachta indica A. Juss.) by anther culture.

Chaturvedi R, Razdan MK, Bhojwani SS.

Department of Plant Molecular Biology, University of Delhi South Campus, Benito
Juarez Road, 110 021 Dhaula Kuan, New Delhi, India. [email protected]

Androgenic haploids of the neem tree (Azadirachta indica A. Juss.) were produced
by anther culture at the early- to late-uninucleate stage of pollen. Haploid
formation occurred via callusing. The best medium for inducing callusing in the
anther cultures was Murashige and Skoog's basal medium (MS) (9% sucrose)
supplemented with 1 microM 2,4-D, 1 microM NAA and 5 microM BAP, while anther
callus multiplied best on MS medium supplemented with 1 microM 2,4-D and 10
microM Kn. These calli differentiated shoots when transferred to a medium
containing BAP; 5 microM BAP was optimum for young calli (75% cultures
differentiated shoots), but older calli showed the best regeneration with 7.5
microM BAP. Shoots elongated at a lower concentration of BAP-0.5 microM. These
shoots were multiplied by forced axillary branching and rooted in vitro. The
plants were subsequently established in soil. Of the plants that regenerated
from anther callus 60% were haploid, 20% were diploid and 20% were aneuploid.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12789427 [PubMed - indexed for MEDLINE]

141: J Basic Clin Physiol Pharmacol. 2002;13(4):311-28.

Ultrastructural changes induced by leaves of Azadirachta indica (Neem) in the
testis of albino rats.

Kasturi M, Ahamed RN, Pathan KM, Manivannan B, Aladakatti RH.

Post-Graduate Department of Zoology Karnatak University, Dharwad 580 003, India.

The present work was designed to study the effect of Azadirachta indica (Neem)
powder on rat testis using the electron microscope. Male albino rats received
100 mg each A. indica leaf powder orally (by gavage). On alternate days, a
second group of rats received 0.125 mg testosterone dipropionate
intramuscularly. A third group received both A. indica leaf powder by gavage and
testosterone dipropionate intramuscularly. Suitable controls were maintained.
After autopsy, ultrastructural analysis of the testis revealed that animals
treated with testosterone dipropionate showed well-developed Sertoli cells and
germ cells with well-developed cytoplasmic organelles. By contrast, in A.
indica-treated rats, intracellular spaces and vacuolization were observed in
Sertoli cells; whereas in Leydig cells, cytoplasmic inclusions appeared
diminished, and the configuration of granular endoplasmic reticulum appeared as
a single unbranched tubule. In late spermatids, defects were observed in the
mitochondrial sheath. The ultrastructural changes seen in the A. indica-treated
group provide a clue that A. indica leaves might affect spermatogenesis through
antispermatogenic and antiandrogenic properties.

PMID: 12751899 [PubMed - indexed for MEDLINE]

142: J Agric Food Chem. 2003 May 7;51(10):2937-42.

6beta-hydroxygedunin from Azadirachta indica. Its potentiation effects with some
non-azadirachtin limonoids in neem against lepidopteran larvae.

Koul O, Multani JS, Singh G, Daniewski WM, Berlozecki S.

Insect Biopesticide Research Centre, 30 Parkash Nagar, Jalandhar-144 003, India.
[email protected]

The biological activity of 6beta-hydroxygedunin isolated from Azadirachta indica
A. Juss. was assessed using the gram pod borer, Helicoverpa armigera (Hubner),
and Asian armyworm, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae),
alone and in combination with other limonoids, gedunin, salannin, nimbinene, and
azadirachtin. The compound exhibited growth inhibitory activity in artificial
diet bioassays, with 24.2 and 21.5 ppm, respectively, inhibiting growth by 50%.
This efficacy was higher in comparison to gedunin (EC(50) = 50.8 and 40.4 ppm),
salannin (EC(50) = 74.5 and 72.0 ppm), and nimbinene (EC(50) = 391.4 and 404.5
ppm). Azadirachtin, however, remained the most active neem allelochemical
against both insect species. Nutritional assays clearly demonstrated that,
though relative consumption and growth rates of fourth instar larvae were
reduced, gedunin-type compounds induced physiological toxicity, evident by
reduced efficiency of conversion of ingested food (ECI) in feeding experiments.
Salannin and nimbinene, on the contrary, induced concentration-dependent feeding
deterrence only. In feeding experiments, combinations of the compounds revealed
that when azadirachtin was present in a mixture, EC(50) values did not deviate
from the individual efficacy of azadirachtin (0.26 and 0.21 ppm, respectively)
against H. armigera and S. litura larvae. However, a combination without
azadirachtin did show a potentiation effect with potent EC(50) values among
structurally different molecules, i.e., when salannin or nimbinene was combined
with 6beta-hydroxygedunin or gedunin rather than structurally similar salannin +
nimbinene or 6beta-hydroxygedunin + gedunin. Obviously, azadirachtin being the
most active compound in neem is not synergized or influenced by any other
limonoid, but other non-azadirachtin limonoids were more potent in specific
combinations vis-a-vis the structural chemistry of the compound. It is obvious
from the present study that potentiation among non-azadirachtin limonoids having
explicitly two different modes of action, such as feeding deterrence and
physiological toxicity, may be playing a significant role in the potentiation

PMID: 12720374 [PubMed - indexed for MEDLINE]

143: Asian Pac J Cancer Prev. 2002;3(3):231-238.

Chemopreventive Potential of Neem Flowers on Carcinogen-Induced Rat Mammary and
Liver Carcinogenesis.

Tepsuwan A, Kupradinun P, Kusamran WR.

Biochemistry and Chemical Carcinogenesis Section, Research Division, National
Cancer Institute, Bangkok 10400, Thailand. [email protected]

We have previously reported that dietary neem flowers (Azadirachta indica A.
Juss var. siamensis Valeton) caused a marked increase in glutathione
S-transferase (GST) activity in the liver, while resulting in a significant
reduction in the activities of some hepatic P450-dependent monooxygenases. These
results strongly indicate that neem flowers may have chemopreventive potential.
In the present study, we examined the inhibitory effects of neem flowers on
9,10-dimethyl-1,2-benzanthracene (DMBA)-induced mammary gland carcinogenesis in
female Sprague Dawley rats and on aflatoxin B(1)(AFB(1))-induced
hepatocarcinogenesis in male Wistar rats. Young animals were fed with AIN-76
purified diets containing either 10-12.5% ground freeze-dried neem flowers for 1
week prior to, during, and for 1 week after the administration of each
carcinogen. Interestingly, it was found that neem flowers resulted in a marked
reduction of the incidence of mammary gland (about 35.2%) and liver tumors
(61.7% and 80.1% for benign and malignant tumors, respectively). Furthermore,
the multiplicity of tumors per rats was also lower in the neem flower groups,
i.e. those for mammary gland tumors and benign and malignant liver tumors were
reduced to 44.0%, 87.9% and 88.9%, respectively. These results clearly
demonstrated that neem flowers contain some chemopreventive agents capable of
inhibiting AFB(1) and DMBA induced liver and mammary gland carcinogenesis in

PMID: 12718580 [PubMed - as supplied by publisher]

144: Meded Rijksuniv Gent Fak Landbouwkd Toegep Biol Wet. 2002;67(3):631-9.

First results of the application of a new Neemazal powder formulation in
hydroponics against different pest insects.

Hummel E, Kleeberg H.

Trifolio-M GmbH, Sonnestr. 22, 35633 Lahnau, Germany.

NeemAzal PC (0.5% Azadirachtin) is a new standardised powder formulation from
the seed kernels of the tropical Neem tree (Azadirachta indica A. Juss) with an
inert carrier. First experiments with beans--as a model-system for
hydroponics--show that active ingredient is taken up by the plants through the
roots and is transported efficiently with the plant sap to the leaves. After
application of NeemAzal PC solution (0.01-1%) to the roots sucking (Aphis fabae
Hom., Aphididae) and free feeding (Heliothis armigera Lep., Noctuidae) pest
insects can be controlled efficiently. The effects are concentration and time

PMID: 12696431 [PubMed - indexed for MEDLINE]

145: Bioresour Technol. 2003 Feb;86(3):267-76.

Medicinal and aromatic plant materials as nitrification inhibitors for
augmenting yield and nitrogen uptake of Japanese mint (Mentha arvensis L. Var.

Kiran U, Patra DD.

Division of Soil Science and Water Technology, Central Institute of Medicinal
and Aromatic Plants, PO CIMAP, Lucknow 226 015, Uttar Pradesh, India.

Pot experiments were conducted to evaluate the relative performance of medicinal
and aromatic plant materials and dicyandiamide (DCD) as nitrification inhibitors
to regulate transformation of N from urea. Their effect on the efficiencies of
use of N by Japanese mint (Mentha arvensis cv. Hy 77) was tested. Urea was
coated with these materials viz., Mentha spicata, Artemisia annua or DCD at the
rate of 5% (w/w) of fertilizer urea using an appropriate coating technique.
Nimin (tetranortriterpenoids, an ethanol extract of neem (Azadirachta indica
Juss) coating was done at the rate of 1% w/w of urea. Fertilizer nitrogen was
applied at 100 and 200 mg kg(-1) soil. These natural coating materials
significantly increased the herb and essential oil yields of the crop at both
rates of fertilizer nitrogen compared to urea alone and were found to be as
effective as DCD in retarding NO3- formation in soil. Herb yield increased by
6-81% when compared to uncoated urea. The increase in essential oil yield ranged
between 3% and 68% due to coating. The effectiveness of the
nitrification-inhibitor--coated urea, however, varied with the soils used and
the rate of fertilizer nitrogen applied. The results suggest that the natural
products could be potential nitrification inhibitors for increasing fertilizer N
use efficiency.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12688470 [PubMed - indexed for MEDLINE]

146: J Ethnopharmacol. 2003 May;86(1):113-6.

Lens aldose reductase inhibiting potential of some indigenous plants.

Halder N, Joshi S, Gupta SK.

Department of Pharmacology, All India Institute of Medical Sciences, Ansari
Nagar, New Delhi 110029, India.

Cataract is the leading cause of blindness worldover. Diabetes is one of the
major risk factors for cataractogenesis and aldose reductase (AR) has been
reported to play an important role in sugar-induced cataract. In the present
study, the AR inhibitory activity of Ocimum sanctum (OS), Withania somnifera
(WS), Curcuma longa (CL), Azadirachta indica (AI) were studied together with
their effect on sugar-induced cataractogenic changes in rat lenses in vitro.
Aqueous extracts of the plants, procured from Dabur, India, were reconstituted
with double distilled water to make various dilutions. AR inhibitory activity of
these extracts and their anticataract potentials were evaluated in vitro in rat
lenses. AR inhibitory activity of the aqueous extract of different plants was
calculated considering the AR activity of normal rat lenses as 100%. The
concentration of the plant extract that showed maximum AR inhibitory activity
was selected to further study its effect on galactose-induced lens swelling and
polyol accumulation in vitro. All the four plants were found to inhibit lens AR
activity but to different extent. From dose-response curve, OS was found to be
the most effective AR inhibitor followed by CL, AI and WS. The IC(50) values of
OS, CL, AI and WS were calculated to be 20, 55, 57 and 89 microg/ml,
respectively. OS showed a significant inhibition (38.05%) in polyol accumulation
followed by CL and AI (28.4 and 25.04%, respectively). WS did not show any
effect on polyol level in rat lenses. None of the plant extracts showed any
significant effect on lens water content.OS possesses a significant anticataract
activity in vitro and its anticataract potential could be related with its AR
inhibitory effect.

PMID: 12686449 [PubMed - indexed for MEDLINE]

147: Chem Pharm Bull (Tokyo). 2003 Apr;51(4):415-7.

Tetracyclic triterpenoids from the leaves of Azadirachta indica and their
insecticidal activities.

Siddiqui BS, Afshan F, Gulzar T, Sultana R, Naqvi SN, Tariq RM.

H. E. J. Research Institute of Chemistry, University of Karachi, Pakistan.
[email protected]

A new tetranortriterpenoid, meliatetraolenone
,20(22)-trien-1,16-dione] (1) was isolated from the methanolic extract of fresh
leaves of Azadirachta indica along with the known compound odoratone (3) which
was hitherto unreported from this source. Their structures have been elucidated
by spectral studies including 2D NMR. The insecticidal activities of 1 as well
as those of odoratone (3) are reported. 1 and odoratone both showed mortality on
fourth instar larvae of mosquitoes (Anopheles stephensi) with LC(50) values of
16 and 154 ppm, respectively.

PMID: 12672995 [PubMed - indexed for MEDLINE]

148: Oral Dis. 2003 Mar;9(2):95-8.

Post-harvest fungal quality of selected chewing sticks.

Etebu E, Tasie AA, Daniel-Kalio LA.

Department of Biological Sciences, Plant Pathology Unit, Rivers State University
of Science and Technology, Rivers State, Port Harcourt, Nigeria.
[email protected]

OBJECTIVE: To study post-harvest fungal overgrowth on chewing sticks used for
oral hygiene measures and role of disinfection. METHODS: The post-harvest fungal
spoilage of chewing sticks (Garcinia kola, Glyphea brevis and Azadirachta
indica) was investigated by subjecting the chewing sticks to different
preparatory methods (some disinfected in 0.7% sodium hypochlorite before
storage), storage conditions (unsealed or sealed in clear polythene) and
different storage periods (2, 3 and 4 weeks). RESULTS: Significant differences
(P = 0.05) in mean percentage fungal colonization were dependent on plant type
and storage period, but not on preparative methods and storage conditions. There
were, however, significant interactions between chewing sticks and preparative
methods, storage conditions and storage periods, respectively. Azadirachta
indica was observed to be more susceptible to post-harvest spoilage organisms
than other test plants. Generally, percentage fungal colonization increased with
increase in storage period. Four genera, Penicillium spp., Aspergillus spp.,
Mucor spp. and Botryodiplodia spp., were implicated with post-harvest
colonization of chewing sticks after 4 weeks of storage. CONCLUSION: The use of
harvested chewing sticks after prolonged storage period is therefore not
advisable for oral hygiene measures.

PMID: 12657036 [PubMed - indexed for MEDLINE]

149: Tree Physiol. 1999 Jan;19(1):47-52.

Variation in net photosynthesis, stomatal characteristics, leaf area and
whole-plant phytomass production among ten provenances of neem (Azadirachta

Kundu SK, Tigerstedt PM.

Department of Plant Biology, P.O. Box 27, FIN-00014 University of Helsinki,

Variation in net photosynthesis, CO(2) exchange parameters, stomatal
characteristics, leaf area and seedling dry weight were investigated among 10
provenances of neem (Azadirachta indica A. Juss.). Significant provenance
variation was established for net photosynthesis (8.14 to 15.13 &mgr;mol m(-2)
s(-1)), stomatal conductance (0.37 to 0.59 mol m(-2) s(-1)), stomatal density
(145 to 204 mm(-2)), and total guard cell length (2681 to 3873 &mgr;m). Net
photosynthesis was positively correlated with whole-plant dry weight and leaf
area. Stomatal density was positively correlated with net photosynthesis,
whole-plant dry weight, and leaf area. Total guard cell length was positively
correlated with all of these traits. Information on six traits was used in a
cluster analysis to construct a dendrogram to assess phenetic relationships
among the provenances. With a few exceptions, the dendrogram revealed three
major clusters grouped according to rainfall distribution. The study indicated
that whole-plant phytomass production of neem seedlings was associated with
photosynthesis and stomatal characteristics during the early stages of growth.

PMID: 12651331 [PubMed - as supplied by publisher]

150: J Ethnopharmacol. 2003 Apr;85(2-3):179-85.

Cultural categorization of febrile illnesses in correlation with herbal remedies
used for treatment in Southwestern Nigeria.

Ajaiyeoba EO, Oladepo O, Fawole OI, Bolaji OM, Akinboye DO, Ogundahunsi OA,
Falade CO, Gbotosho GO, Itiola OA, Happi TC, Ebong OO, Ononiwu IM, Osowole OS,
Oduola OO, Ashidi JS, Oduola AM.

Department of Pharmacognosy, University of Ibadan, Ibadan, Nigeria.
[email protected]

The ethnographic study was conducted in two communities in Oyo State in
Southwestern Nigeria. The study sites consisted of a rural and an urban local
government area located in the tropical rain forest zone of Nigeria. The study
was designed to obtain information on febrile illnesses and herbal remedies for
treatment with the aim of identifying potential antimalarial drugs. The study
revealed that fever is a general term for describing illnesses associated with
elevated body temperature. The indigenous Yoruba ethnic population has
categorized fever based on symptoms and causes. The present communication is the
result of focus group discussion and semi-structured questionnaire administered
to traditional healers, herb sellers, elders and mothers. This was on types of
fevers, symptoms and causes of febrile illnesses. The investigation also
included use of traditional herbs in the prevention and treatment of the
illnesses in the two communities.A total of 514 respondents were interviewed.
This was made up of 266 (51.8%) from Atiba local government area (LGA), an urban
centre while 248 (48.2%) respondents were interviewed from Itesiwaju LGA, a
rural community. The LGAs are located in Oyo State of Nigeria. The respondents
proffered 12 types of febrile illnesses in a multiple response answering system
in Yoruba language. The most common ones (direct translation into English) were:
yellow fever (39.1%), typhoid (34.8%), ordinary (28.8%), rainy season (20.8%)
and headache (10.5%) fevers, respectively. Perceived causes of each of the
febrile illnesses included stress, mosquito bites, unclean water, rains and over
exposure to the sun. Methods of fever prevention were mainly with the use of
herbal decoctions, powdered herbs, orthodox medications and maintenance of
proper hygiene.Of a total of 112 different herbal remedies used in the treatment
of the febrile illnesses compiled from the study, 25 recipes are presented.
Recipes consisted of 2-7 ingredients. Oral decoctions (84%), oral powders (63%),
use as soaps and creams (40%) in a multiple response system, were the most
prevalent routes of administration of prepared herbs used in the treatment of
the fevers. Boiling in water or alcohol was the most common method used in the
preparation of the remedies. The four most frequently mentioned (multiple
response system) plants in the Southwest ethnobotany for fevers were Azadirachta
indica (87.5%), Mangifera indica (75.0%), Morinda lucida (68.8%) and Citrus
medica (68.8%).

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12639738 [PubMed - indexed for MEDLINE]

151: Phytomedicine. 2003 Jan;10(1):34-8.

Inhibition of Propionibacterium acnes-induced mediators of inflammation by
Indian herbs.

Jain A, Basal E.

Department of Microbiology, King George's Medical College, Lucknow, India.
[email protected]

Propionibacterium acnes, an anaerobic pathogen, plays an important role in the
pathogenesis of acne by inducing certain inflammatory mediators. These mediators
include reactive oxygen species (ROS) and pro-inflammatory cytokines. In the
present study, ROS, interleukin-8 (IL-8) and tumor necrosis factor-alpha
(TNF-alpha) were used as the major criteria for the evaluation of
anti-inflammatory activity. To prove the anti-inflammatory effects of herbs,
polymorphonuclear leukocytes (PMNL) and monocytes were treated with culture
supernatant of P. acnes in the presence or absence of herbs. It was found that
Rubia cordifolia, Curcuma longa, Hemidesmus indicus, and Azadirachta indica
caused a statistically significant suppression of ROS from PMNL. Sphaeranthus
indicus caused a smaller, still significant suppression of ROS. Aloe vera had no
effect on ROS production. In the case of proinflammatory cytokine-induced
monocytes, maximum suppression was shown by Azadirachta indica and Sphaeranthus
indicus, followed by Hemidesmus indicus, Rubia cordifolia, and Curcuma longa.
Aloe vera showed insignificant inhibitory activity. Thus, these herbs shows
anti-inflammatory activity by suppressing the capacity of P. acnes-induced ROS
and pro-inflammatory cytokines, the two important inflammatory mediators in acne

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12622461 [PubMed - indexed for MEDLINE]

152: Phytochemistry. 2003 Mar;62(5):747-51.

Antiplasmodial and antifungal activities of iridal, a plant triterpenoid.

Benoit-Vical F, Imbert C, Bonfils JP, Sauvaire Y.

Laboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, F-31077
Toulouse Cedex 4, France. [email protected]

Iridal, a triterpenoidic compound extracted from Iris germanica L., was
previously shown to have an interesting activity on two cultured human tumor
cell lines (A2780 and K562). In the present work, this same product was tested
in vitro on Plasmodium falciparum chloroquine-resistant and -sensitive strains,
in vivo on P. vinckei, and on some Candida albicans and C. parapsilosis strains
too. The IC(50) obtained in vitro on human malaria strain ranged from 1.8 to
26.0 microg/ml and the ED(50) in vivo is about 85 mg/kg/day by intraperitoneal
route. The minimal inhibitory concentrations were higher than to 50 microg/ml,
whatever the strain of yeast tested. This product presents an antiplasmodial
activity similar to that obtained with extracts from the plant Azadirachta
indica classically taken as reference in malaria phytomedicine. Conversely
iridal shows no important antifungal activity. The specific activity of iridal
on human malaria parasite and on tumor cell lines is discussed.

PMID: 12620327 [PubMed - indexed for MEDLINE]

153: Curr Top Med Chem. 2003;3(2):133-9.

Traditionally-used antimalarials from the Meliaceae.

Omar S, Zhang J, MacKinnon S, Leaman D, Durst T, Philogene BJ, Arnason JT,
Sanchez-Vindas PE, Poveda L, Tamez PA, Pezzuto JM.

Ottawa-Carleton Institute of Biology, University of Ottawa, Ottawa, ON K1N 6N5,

A quantitative ethnobotanical approach to antimalarial drug discovery led to the
identification of Lansium domesticum Corr. Ser. (Meliaceae) as an important
antimalarial used by Kenyah Dyak healers in Indonesian Borneo. Triterpenoid
lansiolides with antimalarial activity were isolated from the bark and shown to
have activity in both in vitro bioassays with Plasmodium falciparum, and in mice
infected with P. berghei. A survey of African and tropical American Meliaceae
led to further development of the limonoid gedunin from the traditionally used
medicinal plants, tropical cedar, Cedrela odorata L., and neem, Azadirachta
indica A. Juss. Gedunin has significant in vitro activity but initially showed
poor in vivo activity. In vivo activity was improved by (1) incorporation into
an easy to absorb suspension, (2) preparation of a more stable compound,
7-methoxygedunin; and (3) synergism with dillapiol, a cytochrome P450 3A4
inhibitor. The results show the potential for both antimalarial drug and
phytomedicine development from traditionally used plants.

Publication Types:

PMID: 12570769 [PubMed - indexed for MEDLINE]

154: J Agric Food Chem. 2003 Feb 12;51(4):910-5.

Variability in Neem (Azadirachta indica) with respect to azadirachtin content.

Sidhu OP, Kumar V, Behl HM.

National Botanical Research Institute, Lucknow 226001, India.

There is a controversy over variations in azadirachtin content in neem
(Azadirachta indica) seeds among various provenances and countries. Also,
variations in azadirachtins are usually attributed to climatic conditions such
as temperature and humidity. The present study was undertaken to evaluate
qualitative and quantitative variability in azadirachtins A and B among various
neem provenances or individual neem trees. Forty-three provenances of India were
examined for intraprovenance variability in azadirachtin A and B content and oil
percentage. Twenty-eight individual neem trees from five provenances of
different agroclimatic regions were also examined for interprovenance
variability. The azadirachtins were quantified using reversed phase analytical
HPLC. There were wide variations in oil and azadirachtin contents among
different provenances. Azadirachtin A ranged from 556.9 to 3030.8 mg kg(-)(1) of
kernels, whereas azadirachtin B was in the range 43.1-590.6 mg kg(-)(1) of
kernel among the provenances investigated. Analysis of variance among various
neem provenances showed significant differences in oil content, azadirachtin A,
total azadirachtin (A + B), and A:B ratio. There were individuals with high and
low azadirachtins within a single provenance, and this trend was observed in all
of the provenances selected from five agroclimatic regions of the country.
Variations among individual trees of a particular provenance indicated that
climatic factors such as rainfall, humidity, or temperature did not influence
azadirachtin content in the neem trees. The present study shows that there are
individual genetic differences among neem trees. A systematic study for tree
improvement with a population of mother trees with desired traits should be
undertaken by performing half-sib progeny trials and further selections by
clonal propagations. The role of genetic makeup needs further research.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12568548 [PubMed - indexed for MEDLINE]

155: J Appl Toxicol. 2003 Jan-Feb;23(1):19-22.

Effect of single and binary combinations of plant-derived molluscicides on
different enzyme activities in the nervous tissue of Achatina fulica.

Rao IG, Singh A, Singh VK, Singh DK.

Department of Zoology, DDU Gorakhpur University, Gorakhpur, India.

Effect of single and binary treatments of plant-derived molluscicides on
different enzymes--acetylcholinesterase (AChE), lactic dehydrogenase (LDH) and
acid/alkaline phosphatase (ACP/ALP)--in the nervous tissue of the harmful
terrestrial snail Achatina fulica were studied. Sublethal in vivo 24-h exposure
to 40% and 80% LC(50) of Azadirachta indica oil, Cedrus deodara oil, Allium
sativum bulb powder, Nerium indicum bark powder and binary combinations of A.
sativum (AS) + C. deodara (CD) and CD + A. indica (AI) oils significantly
altered the activity of these enzymes in the nervous tissue of Achatina fulica.
The binary treatment of AS + CD was more effective against AChE, LDH, and ALP
than the single ones. However, binary treatment of AI + CD was more effective
against ALP. Copyright 2003 John Wiley & Sons, Ltd.

Publication Types:
In Vitro

PMID: 12518332 [PubMed - indexed for MEDLINE]

156: Indian J Physiol Pharmacol. 2002 Apr;46(2):241-4.

A study of cardiovascular effects of Azadirachta indica (neem) on isolated
perfused heart preparations.

Khosla P, Gupta A, Singh J.

Department of Pharmacology, Pt. B.D. Sharma PGIMS, Rohtak-124 001.

The effects of aqueous leaf extract of Azadirachta indica were evaluated on
isolated prefused frog and rabbit heart. Dose dependent negative inotropic and
chronotropic effects were observed in both the heart preparation. An increase in
coronary blood flow in isolated rabbit heart was observed. The effects were not
blocked by atropine and mepyramine in both the preparations. The data suggests
that A. indica could be of benefit in coronary artery disease and arrhythmias.

Publication Types:
In Vitro

PMID: 12500501 [PubMed - indexed for MEDLINE]

157: J Ethnopharmacol. 2003 Jan;84(1):105-8.

Comparative evaluation of hypoglycaemic activity of some Indian medicinal plants
in alloxan diabetic rats.

Kar A, Choudhary BK, Bandyopadhyay NG.

Satsang Herbal Research and Analytical Laboratories, PO Satsang-814 116 Deoghar,
India. [email protected]

In our experiments 30 hypoglycaemic medicinal plants (known and less known) have
been selected for thorough studies from indigenous folk medicines, Ayurvedic,
Unani and Siddha systems of medicines. In all the experiments with different
herbal samples (vacuum dried 95% ethanolic extracts), definite blood glucose
lowering effect within 2 weeks have been confirmed in alloxan diabetic albino
rats. Blood glucose values are brought down close to normal fasting level using
herbal samples at a dose of 250 mg/kg once, twice or thrice daily, as needed.
While evaluating comparative hypoglycaemic activity of the experimental herbal
samples, significant blood glucose lowering activities are observed in
decreasing order in the following 24 samples-Coccinia indica, Tragia
involucrata, G. sylvestre, Pterocarpus marsupium, T. foenum-graecum, Moringa
oleifera, Eugenia jambolana, Tinospora cordifolia, Swertia chirayita, Momordica
charantia, Ficus glomerata, Ficus benghalensis, Vinca rosea, Premna
integrifolia, Mucuna prurita, Terminalia bellirica, Sesbenia aegyptiaca,
Azadirachta indica, Dendrocalamus hamiltonii, Zingiber officinale, Aegle
marmelos, Cinnamomum tamala, Trichosanthes cucumerina and Ocimum sanctum.
Present studies besides confirming hypoglycaemic activities of the experimental
herbal samples, help identify more potent indigenous hypoglycaemic herbs (in
crude ethanolic extract) from the comparative study of the reported experimental
results. Copyright 2002 Published by Elsevier Science Ireland Ltd.

PMID: 12499084 [PubMed - indexed for MEDLINE]

158: Anal Bioanal Chem. 2002 Dec;374(7-8):1199-204. Epub 2002 Nov 12.

Determination of azadirachtin and fatty acid methyl esters of Azadirachta indica
seeds by HPLC and GLC.

Kaushik N.

Bioresources and Biotechnology Division, TERI, Habitat Place, Lodhi Road, New
Delhi 110 003, India. [email protected]

A simple and economical method has been developed to estimate the azadirachtin
content and fatty acid composition of neem kernels. Neem kernels are crushed and
soaked overnight in ethanol. The extract obtained is analysed by HPLC after
filtering through a 0.22 micro m membrane. The peaks are separated using
acetonitrile-water (40:60) 1 mL min(-1) as the mobile phase on an RP-18 column
and monitored at 214 nm. For the determination of fatty acid composition, the
fatty acids are directly transmethylated in the kernel powder by heating with
methanol-acetyl chloride-benzene (20:1:4, v/v) for 1 h in a water bath. The
fatty acid methyl esters (FAMEs) obtained are extracted in hexane and analysed
using GLC. The separation of the FAMEs is achieved using an RH-Wax column using
temperature programming, 170-200 degrees C at 2 degrees min(-1). The peaks are
detected using an FID. Both the methods do not require any clean up or defatting
of seeds. This results in faster, easier and more economical sample preparation.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12474085 [PubMed - indexed for MEDLINE]

159: Int J Food Microbiol. 2003 Feb 15;80(3):223-30.

Antibacterial activity of extracts from some edible plants commonly consumed in

Alzoreky NS, Nakahara K.

Faculty of Agriculture, Department of Food Science, Sana'a University, Sana'a,

Extracts of edible plants (26 species) from China, Japan, Thailand and Yemen
were screened for their antibacterial activity against Bacillus cereus,
Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella
infantis. Buffered methanol (80% methanol and 20% PBS) and acetone extracted
inhibitory substances against tested bacteria from 16 plants, as revealed by the
disc assay. The minimum inhibitory concentrations (MICs) of extracts determined
by the agar dilution method ranged from 165 to 2640 mg l(-1). The most sensitive
microorganism to extracts from Azadirachta indica, Cinnamomum cassia, Rumex
nervosus, Ruta graveolens, Thymus serpyllum and Zingiber officinale was B.
cereus, with MIC of 165 to 660 mg l(-1). E. coli and S. infantis were only
inhibited by Cinnamomum cassia extracts at the highest MIC (2640 mg l(-1)). L.
monocytogenes (Tottori) was more resistant than the ATCC 7644 strain to extracts
from Ruta chalepensis, Artemisia absinthium and Cissus spp. EDTA (0.85 mM)
reduced the MICs of Cinnamomum cassia and Cissus rotundifolia by at least 50%
when tested against E. coli, S. infantis, S. aureus and L. monocytogenes.
Copyright 2002 Elsevier Science B.V.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12423924 [PubMed - indexed for MEDLINE]

160: Acta Crystallogr C. 2002 Nov;58(Pt 11):o681-2. Epub 2002 Oct 31.


Malathi R, Rajan SS, Gopalakrishnan G, Suresh G.

Department of Crystallography and Biophysics, University of Madras, Guindy
Campus, Chennai 600 025, India.

The title compound, methyl
C(32)H(42)O(8), was isolated from uncrushed green leaves of Azadirachta indica
A. Juss (neem) and has been found to possess antifeedant activity against
Spodptera litura. The conformations of the functional groups are similar to
those of 3-desacetylsalannin, which was isolated from neem kernels. The
molecules are linked into chains by intermolecular O-H.O hydrogen bonds.

PMID: 12415181 [PubMed]

161: Am J Trop Med Hyg. 2002 Aug;67(2):191-5.

Repellency of live potted plants against Anopheles gambiae from human baits in
semi-field experimental huts.

Seyoum A, Kabiru EW, Lwande W, Killeen GF, Hassanali A, Knols BG.

International Centre of Insect Physiology and Ecology, Nairobi, Kenya.
[email protected]

The repellency of potted plants against the malaria vector Anopheles gambiae
sensu stricto Giles was quantified in experimental huts under semi-field
conditions inside a screen-walled greenhouse. Ocimum americanum Linnaeus
(Labiatae), Lantana camara L. (Verbenaceae), and Lippia uckambensis Spreng
(Verbenaceae) repelled at an average of 39.7% (95% confidence interval [CI] =
29.6-48.4%), 32.4% (95% CI = 19.7-43.1%), and 33.3% (95% CI = 21.5-43.3%) of the
mosquitoes, respectively (P < 0.0001 for all treatments). This was determined by
logistic regression, allowing for variations associated with different bait
hosts, sampling huts, and replicate test nights. In contrast, Ocimum
kilimandscharicum Guerke (Labiatae), Ocimum suave Willd. (Labiatae), Corymbia
citriodora Hook (Myrtaceae), Azadirachta indica A. Juss (Meliaceae), Tagetes
minuta L. (Asteraceae), and Hyptis suaveolens Poit. (Lamiaceae) did not
significantly repel mosquitoes. The combination of O. americanum with either L.
camara or L. uckambensis repelled 31.6% (95% CI = 19.7-41.7%) and 45.2% (95% CI
= 34.7-54.0%) of the mosquitoes, respectively (P < 0.0001 for both treatments).
This study is the first to show that live intact plants can reduce domestic
exposure to malaria vector mosquitoes. As such, they may represent a new,
sustainable and readily applicable malaria vector control tool for incorporation
into integrated vector management programs.

Publication Types:
Evaluation Studies
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

PMID: 12389946 [PubMed - indexed for MEDLINE]

162: Life Sci. 2002 Nov 1;71(24):2845-65.

Gastroprotective effect of Neem (Azadirachta indica) bark extract: possible
involvement of H(+)-K(+)-ATPase inhibition and scavenging of hydroxyl radical.

Bandyopadhyay U, Biswas K, Chatterjee R, Bandyopadhyay D, Chattopadhyay I,
Ganguly CK, Chakraborty T, Bhattacharya K, Banerjee RK.

Department of Physiology, Indian Institute of Chemical Biology, 4, Raja S. C.
Mullick road, Kolkata 700032, India.

The antisecretory and antiulcer effects of aqueous extract of Neem (Azadirachta
indica) bark have been studied along with its mechanism of action,
standardisation and safety evaluation. The extract can dose dependently inhibit
pylorus-ligation and drug (mercaptomethylimidazole)-induced acid secretion with
ED(50) value of 2.7 and 2 mg Kg(-1) b.w. respectively. It is highly potent in
dose-dependently blocking gastric ulcer induced by restraint-cold stress and
indomethacin with ED(50) value of 1.5 and 1.25 mg Kg(-1) b.w. respectively. When
compared, bark extract is equipotent to ranitidine but more potent than
omeprazole in inhibiting pylorus-ligation induced acid secretion. In a stress
ulcer model, it is more effective than ranitidine but almost equipotent to
omeprazole. Bark extract inhibits H(+)-K(+)-ATPase activity in vitro in a
concentration dependent manner similar to omeprazole. It offers gastroprotection
against stress ulcer by significantly preventing adhered mucus and endogenous
glutathione depletion. It prevents oxidative damage of the gastric mucosa by
significantly blocking lipid peroxidation and by scavenging the endogenous
hydroxyl radical ((z.rad;)OH)-the major causative factor for ulcer. The
(z.rad;)OH-mediated oxidative damage of human gastric mucosal DNA is also
protected by the extract in vitro. Bark extract is more effective than
melatonin, vitamin E, desferrioxamine and alpha-phenyl N-tert butylnitrone, the
known antioxidants having antiulcer effect. Standardisation of the bioactive
extract by high pressure liquid chromatography indicates that peak 1 of the
chromatogram coincides with the major bioactive compound, a phenolic glycoside,
isolated from the extract. The pharmacological effects of the bark extract are
attributed to a phenolic glycoside which is apparently homogeneous by HPLC and
which represents 10% of the raw bark extract. A single dose of 1g of raw extract
per kg b.w. (mice) given in one day and application of 0.6g raw extract per kg
b.w. per day by oral route over 15 days to a cumulative dose of 9g per kg was
well tolerated and was below the LD(50). It is also well tolerated by rats with
no significant adverse effect. It is concluded that Neem bark extract has
therapeutic potential for the control of gastric hyperacidity and ulcer.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12377267 [PubMed - indexed for MEDLINE]

163: J Nat Prod. 2002 Aug;65(8):1216-8.

Two new triterpenoids from Azadirachta indica and their insecticidal activity.

Siddiqui BS, Afshan F, Faizi S, Naeem-Ul-Hassan Naqvi S, Tariq RM.

H.E.J. Research Institute of Chemistry, International Centre for Chemical
Sciences, University of Karachi, Pakistan. [email protected]

Two new triterpenoids, 22,23-dihydronimocinol (1) and
desfurano-6alpha-hydroxyazadiradione (2), were isolated from a methanolic
extract of the fresh leaves of Azadirachta indica (neem) along with a known
meliacin, 7alpha-senecioyl-(7-deacetyl)-23-O-methylnimocinolide. The structures
of 1 and 2 were elucidated through spectral and chemical studies. Compounds 1
and 2 showed mortality for fourth instar larvae of the mosquito (Anopheles
stephensi), with LC(50) values of 60 and 43 ppm, respectively.

PMID: 12193038 [PubMed - indexed for MEDLINE]

164: J Nat Prod. 2002 Aug;65(8):1177-9.

Three new tetranortriterpenoids from neem seed oil.

Hallur G, Sivramakrishnan A, Bhat SV.

Department of Chemistry, Indian Institute of Technology, Powai, Mumbai 400 076,

Three new tetranortriterpenoids, 1alpha,2alpha-epoxy-17beta-hydroxyazadiradione
(1), 1alpha,2alpha-epoxynimolicinol (2), and 7-deacetylnimolicinol (3), have
been isolated from a methanol extract of neem oil (Azadirachta indica, seed oil)
along with the known compounds epoxyazadiradione, 17beta-hydroxyazadiradione,
gedunin, nimbin, and nimolicinol (4). Spectral studies and chemical
transformations were used to establish the structure of compounds 1-3. The
characterization of the epoxides 1 and 2 in neem oil is of biogenetic
significance, as they may be considered as intermediates between A-ring enones
and 1,3-diols among the A. indica tetranortriterpenoids.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12193026 [PubMed - indexed for MEDLINE]

165: Trans R Soc Trop Med Hyg. 2002 May-Jun;96(3):225-31.

Traditional use of mosquito-repellent plants in western Kenya and their
evaluation in semi-field experimental huts against Anopheles gambiae:
ethnobotanical studies and application by thermal expulsion and direct burning.

Seyoum A, Palsson K, Kung'a S, Kabiru EW, Lwande W, Killeen GF, Hassanali A,
Knols BG.

International Centre of Insect Physiology and Ecology, P.O. Box 30772, Nairobi,
Kenya. [email protected]

Ethnobotanical survey in 2 communities in western Kenya revealed that the most
commonly known repellent plants were Ocimum americanum L. (64.1%), Lantana
camara L. (17.9%), Tagetes minuta L. (11.3%) and Azadirachta indica A. Juss
(8.7%) on Rusinga Island, and Hyptis suaveolens Poit. (49.2%), L. camara (30.9%)
and O. basilicum L. (30.4%) in Rambira. Direct burning of plants is the most
common method of application for O. americanum (68.8%), L. camara (100%) and O.
basilicum (58.8%). Placing branches or whole plants inside houses is most common
for H. suaveolens (33.3 and 57.8% for the respective locations), A. indica (66.7
and 100%), and T. minuta (54.8 and 56.0%). The repellency of plants suggested by
the ethnobotanical survey and other empirical information was evaluated against
the malaria vector Anopheles gambiae s.s. Giles in experimental huts within a
screenwalled greenhouse. Thermal expulsion and direct burning were tested as
alternative application methods for the selected plants O. americanum, O.
kilimandscharicum Guerke, O. suave Willd., L. camara, A. indica, H. suaveolens,
Lippia uckambensis Spreng and Corymbia citriodora Hook. When thermally expelled,
only H. suaveolens failed to repel mosquitoes, whereas the leaves of C.
citriodora (74.5%, P < 0.0001), leaves and seeds of O. suave (53.1%, P < 0.0001)
and O. kilimandscharicum (52.0%, P < 0.0001) were the most effective. Leaves of
C. citriodora also exhibited the highest repellency (51.3%, P < 0.0001) by
direct burning, followed by leaves of L. uckambensis (33.4%, P = 0.0004) and
leaves and seeds of O. suave (28.0%, P = 0.0255). The combination of O.
kilimandscharicum with L. uckambensis repelled 54.8% of mosquitoes (P < 0.0001)
by thermal expulsion. No combination of plants increased repellency by either
method. The semi-field system described appears a promising alternative to
full-field trials for screening large numbers of candidate repellents without
risk of malaria exposure.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

PMID: 12174767 [PubMed - indexed for MEDLINE]

166: J Agric Food Chem. 2002 Aug 14;50(17):4796-802.

Antimutagenicity of some edible Thai plants, and a bioactive carbazole alkaloid,
mahanine, isolated from Micromelum minutum.

Nakahara K, Trakoontivakorn G, Alzoreky NS, Ono H, Onishi-Kameyama M, Yoshida M.

Japan International Research Center for Agricultural Sciences, 1-1 Owashi,
Tsukuba, Ibaraki 305-8686, Japan. [email protected]

The antimutagenic activity against Trp-P-1 of methanolic extracts of 118 samples
(108 species) of edible Thai plants was examined by the Ames Test. The activity
was evaluated by the amount of plant extracts which suppressed 90% of the
mutagenesis (ED90). Five plants, Micromelum minutum, Oroxylum indicum, Cuscuta
chinensis, Azadirachta indica, and Litsea petiolata, exhibited significant
activity with antimutagenic ED90 values lower than 5 microL/plate (0.1 mg of dry
plant material equivalent). The activity-guided fractionation of the extract of
M. minutum, which exhibited the highest antimutagenic activity in the screening,
resulted in the isolation of an active principle, (+)-mahanine (1) as confirmed
by its physicochemical properties. Compound 1 showed a wide variety of
biological activity, including antimutagenicity against heterocyclic amines such
as Trp-P-1 with an IC50 of 5.2 microM, cytotoxicity against a tumor cell line
HL60 with a MIC100 of 4.0 microg/mL, and antimicrobial activity against Bacillus
cereus and Staphylococcus aureus with MIC100 values of 6.25 and 12.5 microg/mL,

PMID: 12166962 [PubMed - indexed for MEDLINE]

167: Mycopathologia. 2002;154(2):79-84.

Effects of neem leaf extract on production of aflatoxins and activities of fatty
acid synthetase, isocitrate dehydrogenase and glutathione S-transferase in
Aspergillus parasiticus.

Allameh A, Razzaghi Abyane M, Shams M, Rezaee MB, Jaimand K.

Faculty of Medical Sciences, Tarbiat Modaress University, Tehran, I.R. Iran.
[email protected]

The relationship between the activities of 3 cytosolic enzymes with aflatoxin
biosynthesis in Aspergillus parasiticus cultured under different conditions has
been investigated in order to find out the role of each enzyme in aflatoxin
biosynthesis. Basically the activity of isocitrate dehydrogenase (IDH) was
higher in non-toxigenic strains as compared to its counterpart toxigenic fungi
(p < 0.05). In contrast, the activities of fatty acid synthase (FAS) as well as
glutathione S-transferase (GST) were higher (P < 0.05) in toxigenic strains than
that of the non-toxigenic fungi. Aflatoxin production was inhibited in fungi
grown in presence of various concentrations of neem leaf extract. Aflatoxin was
at its lowest level (>90% inhibition) when the concentration of neem extract was
adjusted to 50% (v/v). No significant changes in FAS and IDH activities were
observed when aflatoxin synthesis was under restraints by neem (Azadirachta
indica) leaf extract. During a certain period of time of culture growth, when
aflatoxin production reached to its maximum level, the activity of FAS was
slightly induced in the toxigenic strains fed with a low concentration (1.56%
v/v) of the neem leaf extract. At the time (96 h) when aflatoxin concentration
reached to its maximum levels, the activity of GST in the toxigenic fungi was
significantly higher (i.e., 7-11 folds) than that of non-toxigenic strains. The
difference was highest in mycelial samples collected after 120 h. However unlike
FAS and IDH, GST was readily inhibited (approximately 67%) in mycelia fed with
1.56% v/v of the neem extract. The inhibition reached to maximum of 80% in
samples exposed to 6.25-12.5% of the extract. These results further substantiate
previous finding that there is a positive correlation between GST activity and
aflatoxin production in fungi.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12086104 [PubMed - indexed for MEDLINE]

168: J Environ Sci Health A Tox Hazard Subst Environ Eng. 2002;37(5):893-904.

Studies on the use of neem products for removal of ammonia from brackishwater.

Krishnani KK, Gupta BP, Joseph KO, Muralidhar M, Nagavel A.

Central Institute of Brackishwater Aquaculture, R. A. Puram, Chennai, India.
[email protected]

Laboratory experiments were carried out to investigate the ammonia removal from
brackishwater (Salinity 16 +/- 1 ppt) using natural plant products such as seed
powder and seed oil from neem (Azadirachta indica) and commercially available
neem products-neemazal and neemgold. The experimental results showed that
ammonia removal was effective with 90 mg/l of neem oil, whereas, neem seed
powder at 90 mg/l registered an increase in ammonia levels throughout the course
of the experiment. Neem oil, neemazal, and neemgold at 90 mg/l were effective in
decreasing the total ammonia nitrogen (TAN) level of 0.40-0.45 mg/l in 96 h. The
effect of initial ammonia concentrations on the ammonia removal using neem oil
revealed that percentage ammonia removal decreased with an increase in initial
ammonia concentration.

PMID: 12049123 [PubMed - indexed for MEDLINE]

169: Hindustan Antibiot Bull. 1999 Feb-Nov;41(1-4):22-4.

In vitro evaluation on inhibitory nature of some Neem formulations against plant
pathogenic fungi.

Bhonde SB, Deshpande SG, Sharma RN.

Entomology Section, National Chemical Laboratory, Pune 411 007, India.

Different Neem formulations derived from the Neem tree (Azadirachta indica) have
been found to be potential fungicides against a broad spectrum of plant
pathogenic fungi. Some Neem formulations viz. Achook (0.15% EC), Bioneem (0.03%
EC), Nimbecidine (0.03% EC) and Neemark (0.03% EC) were examined against some
plant pathogenic fungi such as (Fusarium oxysporum, Alternaria solani,
Curvularia lunata, Helminthosporium sp. and Sclerotium rolfsii). Among these
Achook (0.15% EC) was found to be more active in terms of Minimum Inhibition
Concentration (MIC) value followed by Bioneem, Neemark and Nimbecidine.
Remarkably, although all these formulations are oil based, Neem oil itself did
not exhibit any fungicidal activity.

PMID: 12024976 [PubMed - indexed for MEDLINE]

170: Vet Parasitol. 2002 May 30;106(1):89-96.

In vitro acaricidal effect of plant extract of neem seed oil (Azadirachta
indica) on egg, immature, and adult stages of Hyalomma anatolicum excavatum
(Ixodoidea: Ixodidae).

Abdel-Shafy S, Zayed AA.

Parasitology and Animal Diseases Department, National Research Center, P.O. Box
12622, Dokki, Giza, Egypt.

Effects of the plant extract of neem seed (Azadirachta indica) on eggs,
immature, and adult stages of Hyalomma anatolicum excavatum was studied at
concentrations of 1.6, 3.2, 6.4, and 12.8%. The extract was found to have a
significant effect on the hatching rate of eggs. It significantly increased the
hatching rate during the first 7 days post-treatment (DPT) giving incompletely
developed and dead larvae; however, it cause hatching failure at DPT 15. Neem
Azal F induced a significant increased in mortality rates of newly hatched
larvae, unfed larvae, and unfed adults reaching 100% on 15th, 3rd, and 15th DPT,
respectively. The mortality rates increased with the extract concentrations.
Although, it had no significant effect on the moulting rates of fed nymphs, it
caused malformation or deformities in 4% of adults moulted. It was concluded
that the concentration of Neem Azal F which may be used for commercial control
of this tick species were 1.6 and 3.2%.

PMID: 11992715 [PubMed - indexed for MEDLINE]

171: Indian J Dent Res. 2001 Jul-Sep;12(3):133-44.

Erratum in:
Indian J Dent Res 2001 Oct-Dec;12(4):193.

The effect of indigenous Neem Azadirachta indica [correction of (Adirachta
indica)] mouth wash on Streptococcus mutans and lactobacilli growth.

Vanka A, Tandon S, Rao SR, Udupa N, Ramkumar P.

Dept. of Pedodontics & Preventive Dentistry, College of Dental Surgery, Manipal
570 119, India.

Neem is one of the most widely researched tropical tree, with almost all it's
parts being put for a variety of uses. In the present study, the antibacterial
effect of Neem mouthwash against salivary levels of streptococcus mutans and
lactobacillus has been tested over a period of 2 months. Also it's effect in
reversing incipient carious lesions was assessed. While streptococcus mutans was
inhibited by Neem mouthwashes, with or without alcohol as well as chlorhexidine,
lactobacillus growth was inhibited by chlorhexidine alone. The initial data
appears to prove it's effect in inhibiting S. mutans and reversing incipient
carious lesions, longer term clinical trials are essential.

Publication Types:
Clinical Trial
Comparative Study
Randomized Controlled Trial

PMID: 11808064 [PubMed - indexed for MEDLINE]

172: Phytother Res. 2002 Feb;16(1):74-7.

Radiosensitizing effects of neem (Azadirachta indica) oil.

Kumar A, Rao AR, Kimura H.

Radiation and Cancer Biology Laboratory, University of Rajasthan, Jaipur, India.

Radiosensitization by neem oil was studied using Balbc/3T3 cells and SCID cells.
Neem oil enhanced the radiosensitivity of the cells when applied both during and
after x-irradiation under aerobic conditions. Neem oil completely inhibited the
repair of sublethal damage and potentially lethal damage repair in Balbc/3T3
cells. The cytofluorimeter data show that neem oil treatment before and after
x-irradiation reduced the G(2) + M phase, thus inhibiting the expression of the
radiation induced arrest of cells in the G(2) phase of the cell cycle. However,
SCIK cells (derived from the SCID mouse), deficient in DSB repair, treated with
neem oil did not show any enhancement in the radiosensitivity. There was no
effect of neem oil on SLD repair or its inhibition in SCIK cells. These results
suggest that neem oil enhanced the radiosensitivity of cells by interacting with
residual damage after x-irradiation, thereby converting the sublethal damage or
potentially lethal damage into lethal damage, inhibiting the double-strand break
repair or reducing the G(2) phase of the cell cycle. Copyright 2002 John Wiley &
Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11807971 [PubMed - indexed for MEDLINE]

173: J Ethnopharmacol. 2002 Feb;79(2):273-8.

Inhibitory potential of neem (Azadirachta indica Juss) leaves on dengue virus
type-2 replication.

Parida MM, Upadhyay C, Pandya G, Jana AM.

Division of Virology, Defence Research and Development Establishment, Gwalior
474 002, MP, India. [email protected]

In the present study we report in vitro and in vivo inhibitory potential of
crude aqueous extract of neem leaves and pure neem compound (Azadirachtin) on
the replication of Dengue virus type-2. In vitro antiviral activity of aqueous
neem leaves extract assessed in C(6/36) (cloned cells of larvae of Aedes
albopictus) cells employing virus inhibition assay showed inhibition in dose
dependent manner. The aqueous extract of neem leaves at its maximum non-toxic
concentration of 1.897 mg/ml completely inhibited 100-10,000 TCID(50) of virus
as indicated by the absence of cytopathic effects. The in vivo protection
studies with neem leaves extract at its maximum non-toxic concentrations 120-30
mg/ml resulted in inhibition of the virus replication as confirmed by the
absence of Dengue related clinical symptoms in suckling mice and absence of
virus specific 511 bp amplicon in RT-PCR. The pure neem i.e. Azadirachtin did
not reveal any inhibition on Dengue virus type-2 replication in both in vitro
and in vivo systems.

PMID: 11801392 [PubMed - indexed for MEDLINE]

174: Boll Chim Farm. 2001 Sep-Oct;140(5):367-70.

Effect of Azadirachta indica extract on plasma lipid levels in human malaria.

Njoku OU, Alumanah EO, Meremikwu CU.

Lipid and Lipoprotein Research Unit, Department of Biochemistry, University of
Nigeria, Nsukka, Nigeria.

Plasma lipid levels (cholesterol, HDL-cholesterol, LDL-cholesterol, and
triacylglycerol) were estimated in patients with different antimalarial drugs.
The lipid levels especially cholesterol and LDL-cholesterol were found to be
lower (p > 0.01) during therapy when compared to the control group (non-malaria
patients), while triacylglycerol and HDL-cholesterol levels were higher (p <
0.01) in the malaria patients than the control group.

PMID: 11680094 [PubMed - indexed for MEDLINE]

175: J Agric Food Chem. 2001 Oct;49(10):4584-8.

Influence of operating parameters on the use of the microwave-assisted process
(MAP) for the extraction of azadirachtin-related limonoids from neem
(Azadirachta indica) under atmospheric pressure conditions.

Dai J, Yaylayan VA, Raghavan GS, Pare JR, Liu Z, Belanger JM.

Department of Food Science and Agricultural Chemistry and Department of
Agricultural and Biosystems Engineering, Macdonald Campus of McGill University,
21,111 Lakeshore, Ste-Anne-de-Bellevue, Quebec, H9X 3V9, Canada.

The use of the microwave-assisted process (MAP) for the extraction of
azadirachtin-related limonoids (AZRL) from various parts of the neem tree was
investigated under different operating conditions. The influence of microwave
power, solvent, and irradiation time on the recovery of AZRL was studied. The
efficiency of the microwave-assisted extraction (MAE) of the seed kernel, the
seed shell, the leaf, and the leaf stem was compared to that of conventional
extraction methods. The content of AZRL in the extracts was estimated with a
vanillin-based colorimetric assay and a multivariate calibration technique. The
results showed that the MAE technique can enhance the extraction of AZRL from
different parts of neem possessing microstructures. Investigation of the
influence of the solvent also indicted that the solvent used not only influences
the efficiency but also affects the selectivity of the MAE.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11599992 [PubMed - indexed for MEDLINE]

176: Indian J Med Res. 2001 Apr;113:135-41.

Spermicidal & contraceptive properties of Praneem polyherbal pessary.

Raghuvanshi P, Bagga R, Malhotra D, Gopalan S, Talwar GP.

Talwar Research Foundation, New Delhi, India.

BACKGROUND & OBJECTIVES: Though a number of barrier methods and potent
spermicides are available, most of these have nonoxynol-9 (N-9) as the active
ingredient which is observed to cause inflammation and genital ulceration on
repeated use. The present study was undertaken to develop a safe spermicide with
conjoint microbicidal properties. METHODS: A polyherbal pessary was formulated
with purified ingredients from neem (Azadirachta indica) leaves, Sapindus
mukerossi (pericarp of fruit) and Mentha citrata oil. Spermicidal action on
human sperm was tested by Sander-Cramer slide test in vitro and by post coital
tests in vivo. Contraceptive action was tested in rabbits. RESULTS: The
combination of the three herbal ingredients resulted in the potentiation of the
spermicidal action by 8-folds. The post coital tests confirmed the spermicidal
properties of the Praneem polyherbal pessary (PPP) in women with high cervical
mucous score around mid estrus. It also prevented in most women the migration of
sperm into the cervical mucous. In 15 rabbits studied pregnancy was prevented by
the intravaginal administration of PPP, whereas 13 of the 15 animals in the
control group became pregnant. INTERPRETATION & CONCLUSION: The Praneem
polyherbal pessary has potent spermicidal action on human sperm in vitro and in
vivo. When applied in the vagina before mating, it prevented rabbits from
becoming pregnant.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11558322 [PubMed - indexed for MEDLINE]

177: Cytobios. 2001;106 Suppl 2:151-64.

Genotoxicity of a crude leaf extract of neem in male germ cells of mice.

Awasthy KS.

Department of Zoology, K.K.M. College, Pakur, India.

The oral administration of a soxhlated crude ethanolic extract of leaves of neem
(Azadirachta indica Ajuss; family Meliaceae) to adult male mice for 6 weeks (one
spermatogenic duration) at the rate of 0.5, 1.0 or 2.0 g/kg body weight per day
increased the incidences of structural changes and synaptic-disturbances in
meiotic chromosomes and also caused more disruptions of meiosis. The extract
reduced the sperm count and increased the frequency of spermatozoa with abnormal
head morphology. It is suggested that at least one of the constituents of the
extract may have interfered with the DNA. The result was chromosome strand
breakages, or spindle disturbances, and the regulation of genes responsible for
sperm shaping was affected.

PMID: 11545443 [PubMed - indexed for MEDLINE]

178: Chemosphere. 2001 Sep;44(8):1691-5.

Combinations of Azadirachta indica and Cedrus deodara oil with piperonyl
butoxide, MGK-264 and Embelia ribes against Lymnaea acuminata.

Rao IG, Singh DK.

Department of Zoology, DDU Gorakhpur University, UP, India.

The binary and tertiary combinations of plant-derived molluscicides Azadirachta
indica and Cedrus deodara oil with synergists MGK-264, piperonyl butoxide (PB)
and fruit powder of Embelia ribes were used against the Lymnaea acuminata. It
was observed that the toxic effects of these mixtures were time- and
dose-dependent. The binary and tertiary mixtures of plant-derived molluscicides
with synergists were more toxic with respect to the single treatment of the
plant-derived molluscicides. Maximum synergistic action in binary and tertiary
combinations was found in A. indica + C. deodara oil and A. indica+ PB + C.
deodara in 1:7 and 1:5:7 ratio, respectively.

PMID: 11534900 [PubMed - indexed for MEDLINE]

179: J AOAC Int. 2001 Jul-Aug;84(4):1001-10.

Erratum in:
J AOAC Int 2001 Nov-Dec;84(6):116A.

Determination of azadirachtin in agricultural matrixes and commercial
formulations by enzyme-linked immunosorbent assay.

Hemalatha K, Venugopal NB, Rao BS.

Osmania University, University College of Science, Department of Biochemistry,
Hyderabad, India.

An enzyme-linked immunosorbent assay (ELISA) was developed for azadirachtin
(aza), a biopesticide from the neem tree (Azadirachta indica A. Juss). The
immunogen was synthesized by epoxidation using the furan ring in the aza
molecule. Rabbits were immunized with either bovine serum albumin
(BSA)-azadirachtin or ovalbumin (OA)-azadirachtin conjugate. Evaluation of the
antisera by antibody capture assay showed that the antibody titer of antisera
raised against OA-aza was 1:30,000. An indirect competitive ELISA was developed
with BSA-azadirachtin as coating antigen and aza-specific antibodies raised
against OA-aza immunogen. The immunoassay showed an inhibitory concentration
(IC50) value of 75 ppb, with a range of detection from 0.5 to 1,000 ppb for
azadirachtin [based on regression analysis, y= 85.87 (-18.89x); r2 = -0.97].
Cross-reactivity of the antibodies with 2 aza- derivatives
(22,23-dihydro-23beta-methoxy azadirachtin and 3-tigloylazadirachtol) was 33 and
29%, respectively. The indirect competitive ELISA was validated and evaluated by
quantitating aza in spiked agricultural commodities and from neem formulations.
Azadirachtin was spiked into 5 different agricultural commodities: tomato,
brinjal, coffee, tea, and cotton seed at 500 and 1,000 ppb and recovered at
62-100%. In samples drawn from 6 lots, the aza content in neem-seed kernels
ranged from 0.1 to 0.15%; in commercial neem formulations the content ranged
from 200 to 2,000 ppm. The method developed may be applied to environmental
monitoring of aza and quality assurance studies of aza-based commercial

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11501897 [PubMed - indexed for MEDLINE]

180: Indian J Exp Biol. 2001 Mar;39(3):263-8.

Molluscicidal activity of Lawsonia inermis and its binary and tertiary
combinations with other plant derived molluscicides.

Singh A, Singh DK.

Department of Zoology, DDU Gorakhpur University, India.

Molluscicidal activity of leaf, bark and seed of Lawsonia inermis against
Lymnaea acuminata and Indoplanorbis exustus was studied. Highest toxicity was
observed in the seed of Lawsonia inermis. Toxicity of binary (1:1) and tertiary
(1:1:1) combinations of the essential oil of cedar (Cedrus deodara Roxh) and
neem (Azadirachta indica A. Juss), powder from bulb of garlic (Allium sativum
Linn), and oleoresin extracted from rhizome of ginger (Zingiber officinale Rosc)
with Lawsonia inermis and Embelia ribes fruit powder were studied against L.
acuminata and I. exustus. L. inermis seed powder in combination with Cedrus
deodara oil and Azadirachta indica oil was more toxic than their individual
components and other combinations.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11495286 [PubMed - indexed for MEDLINE]

181: J Environ Biol. 2001 Jan;22(1):59-66.

Effect of textile industrial effluent on tree plantation and soil chemistry.

Singh G, Bala N, Rathod TR, Singh B.

Division of Forest Ecology and Desert Development, Arid Forest Research
Institute, New Pali Road, Jodhpur-342 005, India.

A field study was conducted at Arid Forest Research Institute to study the
effect of textile industrial effluent on the growth of forest trees and
associated soil properties. The effluent has high pH, electrical conductivity
(EC), sodium adsorption ratio (SAR) and residual sodium carbonate (RSC) whereas
the bivalent cations were in traces. Eight months old seedlings of Acacia
nilotica, Acacia tortilis, Albizia lebbeck, Azadirachta indica, Parkinsonia
aculeata and Prosopis juliflora were planted in July 1993. Various treatment
regimes followed were; irrigation with effluent only (W1), effluent mixed with
canal water in 1:1 ratio (W2), irrigation with gypsum treated effluent (W3),
gypsum treated soil irrigated with effluent (W4) and wood ash treated soil
irrigated with effluent (W5). Treatment regime W5 was found the best where
plants attained (mean of six species) 173 cm height, 138 cm crown diameter and
9.2 cm collar girth at the age of 28 months. The poorest growth was observed
under treatment regime of W3. The growth of the species varied significantly and
the maximum growth was recorded for P. juliflora (188 cm height, 198 cm crown
diameter and 10.0 cm collar girth). The minimum growth was recorded for A.
lebbeck. Irrigation with effluent resulted in increase in percent organic matter
as well as in EC. In most of the cases there were no changes in soil pH except
in W5 where it was due to the effect of wood ash. Addition of wood ash
influenced plant growth. These results suggest that tree species studied (except
A. lebbeck) can be established successfully using textile industrial wastewater
in arid region.

PMID: 11480353 [PubMed - indexed for MEDLINE]

182: Hum Exp Toxicol. 2001 May;20(5):243-9.

Effects of Vepacide (Azadirachta indica) on aspartate and alanine
aminotransferase profiles in a subchronic study with rats.

Rahman MF, Siddiqui MK, Jamil K.

Biology Division, Indian Institute of Chemical Technology, Hyderabad.

The aim of this study was to ascertain the long-term effects of Vepacide, a
neem-based pesticide on biochemical profiles. Albino Wistar rats were treated
orally with 80 (low), 160 (medium) and 320 mg/kg (high) doses of Vepacide in
coconut oil for 90 days. Control rats received the same volume of the vehicle.
Vepacide caused increase of aspartate and alanine aminotransferase in serum,
kidney and lung, and these enzymes decreased in liver in both male and female
rats when measured after 45 and 90 days of treatment. The two-way analysis of
variance (ANOVA) showed that the alterations in these enzymes were dose- and
time-dependent. Sexual dimorphism was observed when male rats were compared with
female rats (Student t-test at P< 0.05). Positive correlation was observed with
regard to these enzymes between serum, kidney and lung, whereas in the case of
serum and liver, a negative correlation was recorded. These enzyme profiles
elucidate that they increased in serum with simultaneous decrease in liver,
indicating necrosis of liver, whereas in other tissues, the level of enzymes
increased, showing an adaptive mechanism due to the chemical stress. The
affected enzymes were recovered to normal conditions after 28 days of
post-treatment (withdrawal study). Due to the Vepacide treatment, lung was more
affected followed by liver and kidney. This study has indicated that these
enzymes could be useful as biomarkers for the insult of any toxicant. Besides,
they can also help in predictive toxicology.

PMID: 11476156 [PubMed - indexed for MEDLINE]

183: J Exp Bot. 2001 May;52(358):919-31.

Viability loss of neem (Azadirachta indica) seeds associated with membrane phase

Sacande M, Golovina EA, van Aelst AC, Hoekstra FA.

Centre National de Semences Forestieres, BP 2682, Ouagadougou, Burkina Faso.

Storage of neem (Azadirachta indica) seeds is difficult because of their
sensitivity to chilling stress at moisture contents (MC) > or =10% or
imbibitional stress below 10% MC. The hypothesis was tested that an elevated
gel-to-liquid crystalline phase transition temperature (Tm) of membranes is
responsible for this storage behaviour. To this end a spin probe technique,
Fourier transform infrared microspectroscopy, and electron microscopy were used.
The in situ Tm of hydrated membranes was between 10 degrees C and 15 degrees C,
coinciding with the critical minimum temperature for germination. During
storage, viability of fresh embryos was lost within two weeks at 5 degrees C,
but remained high at 25 degrees C. The loss of viability coincided with an
increased leakage of K+ from the embryos upon imbibition and with an increased
proportion of cells with injured plasma membranes. Freeze-fracture replicas of
plasma membranes from chilled, hydrated axes showed lateral phase separation and
signs of the inverted hexagonal phase. Dehydrated embryos were sensitive to
soaking in water, particularly at low temperatures, but fresh embryos were not.
After soaking dry embryos at 5 degrees C (4 h) plus 1 d of further incubation at
25 degrees C, the axis cells were structurally disorganized and did not become
turgid. In contrast, cells had a healthy appearance and were turgid after
soaking at 35 degrees C. Imbibitional stress was associated with the loss of
plasma membrane integrity in a limited number of cells, which expanded during
further incubation of the embryos at 25 degrees C. It is suggested that the
injuries brought about by storage or imbibition at sub-optimal temperatures in
tropical seeds whose membranes have a high intrinsic Tm (10-15 degrees C), are
caused by gel phase formation.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11432909 [PubMed - indexed for MEDLINE]

184: J Basic Clin Physiol Pharmacol. 2001;12(1):69-76.

Sperm parameters changes induced by Azadirachta indica in albino rats.

Aladakatti RH, Nazeer Ahamed R, Ahmed M, Ghosesawar MG.

Post-Graduate Department of Zoology, Karnatak University, Dharwad, India.

Azadirachta indica treatment for 48 days In albino rats resulted in a decrease
in the total sperm count, sperm motility, and forward velocity. The percentage
of abnormal sperm increased and the fructose content of caudal semen of the
epididymis decreased. The observations suggest that these effects are probably
due to an androgen deficiency, caused by the anti-androgenic property of the
leaves of A. indica, thereby affecting the physiological maturation of sperm.

PMID: 11414509 [PubMed - indexed for MEDLINE]

185: Microbios. 2001;105(412):183-9.

Antibacterial activity of Karanj (Pongamia pinnata) and Neem (Azadirachta
indica) seed oil: a preliminary report.

Baswa M, Rath CC, Dash SK, Mishra RK.

Centre of Post Graduate Studies in Microbiology, Orissa University of
Agriculture and Technology, Bhubaneswar, India.

The antibacterial activity of Karanj (Pongamia pinnata) and Neem (Azadirachta
indica) seed oil in vitro against fourteen strains of pathogenic bacteria was
assessed. Using the tube dilution technique, it was observed that 57.14 and
21.42% of the pathogens were inhibited at 500 microl/ml; 14.28 and 71.42% at 125
microl/ml; and 28.57 and 7.14% at 250 microl/ml of Karanj and Neem oils,
respectively. The activity with both the oils was bactericidal and independent
of temperature and energy. Most of the pathogens were killed more rapidly at 4
degrees C than 37 degrees C. The activity was mainly due to the inhibition of
cell-membrane synthesis in the bacteria.

PMID: 11414503 [PubMed - indexed for MEDLINE]

186: Indian J Exp Biol. 2000 Nov;38(11):1092-6.

Immunostimulatory effect of azadirachtin in Oreochromis mossambicus (Peters).

Logambal SM, Michael RD.

Fish Immunology Laboratory, Postgraduate and Research Department of Zoology,
American College, Madurai 625 002.

The effect of azadirachtin, a triterpenoid derived from Azadirachta indica on
the immune response was studied in the freshwater teleost, O. mossambicus.
Bovine serum albumin (BSA) and sheep erythrocytes (SRBC) were used as antigens
to evoke immune response. The immune responses in fish were measured by
quantifying antibodies produced and counting the peripheral blood leucocytes in
control and experimental fish. In general, azadirachtin significantly enhanced
the antibody response and leucocyte count in a dose dependent manner. An inverse
relationship was observed between the dose of azadirachtin and the degree of
immunostimulation. Timing of azadirachtin administration in relation to
immunization revealed that the maximum enhancement of antibody response was
observed when the stimulant was given two days prior to immunization. The
observed immunostimulatory property of azadirachtin has an implication in the
maintenance of finfish health in freshwater intensive aquaculture practices.

PMID: 11395951 [PubMed - indexed for MEDLINE]

187: Environ Int. 2000 Aug;26(1-2):11-6.

Pb, Zn, and Cu levels in tree barks as indicator of atmospheric pollution.

Odukoya OO, Arowolo TA, Bamgbose O.

Department of Chemical Sciences, University of Agriculture, Abeokuta, Nigeria.

Barks of seven species of trees were sampled at 32 locations having different
pollution levels in Abeokuta, Nigeria. The concentrations of Pb, Zn, and Cu were
determined by atomic absorption spectrometry. The Pb and Zn contents, 1.9-159.8
and 16.5-659.1 micrograms g-1, dry weight respectively, correlate with traffic
volume, indicating pollution from anthropogenic sources. The results obtained
for Cu, 4.2-20.7 micrograms g-1, dry weight, though lower, were still
significant but did not show any correlation with traffic density. The study
also confirms the suitability of Azadirachta indica (Dogoyaro--a very popular
local tree) as a suitable bio-indicator of aerial fallout of heavy metals.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11345732 [PubMed - indexed for MEDLINE]

188: Biochem Soc Trans. 2000 Dec;28(6):880-2.

Variations in fatty acid composition of neem seeds collected from the Rajasthan
state of India.

Kaushik N, Vir S.

Bioresources and Biotechnology Division, TERI, Darbari Seth Block, Habitat
Place, Lodhi Road, New Delhi 110003, India. [email protected]

Neem (Azadirachta indica) is a multipurpose tree native to the Indian
subcontinent and South-East Asian countries. Products derived from neem have
been used for centuries, particularly in India, for medicinal and
pest-management purposes. Azadirachtin and neem oil are the two major
commercially important products derived from the tree. The oil contains
palmitic, stearic, oleic and linoleic acids in good proportion. Although there
is growing demand for quality planting material for plantation of neem, efforts
are lacking for the selection of neem trees based on their biochemical
composition. In the present study, 60 Neem seed samples were collected from
different provinances of the Rajasthan state in India. These samples were
analysed by GLC to study the variability of fatty acid composition. Significant
variability in individual fatty acids was observed. The palmitic acid ranged
from 16 to 34%, stearic acid from 6 to 24%, oleic acid from 25 to 58% and
linoleic acid from 6 to 17%. This variability can be exploited for selection of
trees and for studying the genetic variability in neem. These selections can
also be utilized for genetic improvement of the tree.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11171243 [PubMed - indexed for MEDLINE]

189: Plant Foods Hum Nutr. 2000;55(4):279-84.

Post harvest physiconutritional changes in Kagzi limes (Citrus aurantifolia
Swingle) treated with selected oil emulsions and diphenyl.

Verma P, Dashora LK.

Department of Horticulture, Rajasthan Agricultural University, Rajasthan College
of Agriculture, Udaipur, India.

Influence of oil emulsions and diphenyl on post-harvest physiconutritional
changes in Kagzi limes (Citrus aurantifolia) was studied. During twelve days of
storage, physiological loss in weight (PLW) and rotting were at a minimum in
fruits treated with Neem (Azadirachta indica A. Juss.) oil plus diphenyl; juice
content was at a maximum in mustard oil + diphenyl treated fruits. With the
advancement of storage period, total soluble solids were increased while
ascorbic acid and acidity of fruits decreased. Mustard oil plus diphenyl
supported maximum ascorbic acid (25.60 mg/100 ml juice) and minimum total
soluble solids (9.03%).

PMID: 11086872 [PubMed - indexed for MEDLINE]

190: Fitoterapia. 2000 Dec;71(6):668-72.

A new triterpenoid from Azadirachta indica.

Luo XD, Wu SH, Ma YB, Wu DG.

Laboratory of Phytochemistry, Kunming Institute of Botany, The Chinese Academy
of Sciences, Kunming 650204, Yunnan, PR China.

A new triterpenoid, 1 alpha,7 alpha-diacetoxyapotirucall-14-en e-3 alpha,
21,22,24,25-pentaol (1), and the two known compounds odoratone (2) and 2 beta,3
beta,4 beta-trihydroxypregnan-16-o ne (3) were isolated from a methanolic
extract of the seed kernels of Azadirachta indica. Their structures were
elucidated on the basis of spectral methods.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11077174 [PubMed - indexed for MEDLINE]

191: Int J Dermatol. 2000 Sep;39(9):689-94.

A study of cutaneous myiasis in Sri Lanka.

Kumarasinghe SP, Karunaweera ND, Ihalamulla RL.

General Hospital, Kalutara, and Department of Parasitology, Faculty of Medicine,
University of Colombo, Colombo, Sri Lanka. [email protected]

BACKGROUND AND OBJECTIVES:Cutaneous myiasis (CM) due to Diptera fly larvae shows
different patterns in different regions. Many modalities of treatment have been
described. The objectives of our study were to identify the species causing CM
in Sri Lanka, the common sites of infestation, and the contributory factors, and
to assess some treatment modalities, in particular mineral turpentine and
certain herbal preparations. METHODS: All patients with CM admitted or referred
to the Dermatology Unit at the General Hospital, Kalutara, over 18 months
starting from July 1997, and all patients with CM from the orthopedic and
surgical wards of the National Hospital of Sri Lanka in Colombo over 6 months
from July 1997, were studied. Details of the history and examination were
recorded on specially designed forms. Maggots extracted were identified at the
Department of Parasitology, Faculty of Medicine, University of Colombo. The
modalities of treatment employed in the patients were recorded. In the
Department of Parasitology, a colony of Chrysomya megacephala was maintained.
Homogenized leaf extracts of Azadirachta indica (neem) and Pongamia pinnata
(Indian beech) and mineral turpentine (active ingredient--low aromatic white
spirits) were tested for efficacy in killing C. megacephala larvae in vitro.
Leaf extracts were not used directly on patients. RESULTS: There were 16
patients (10 males and five females; the sex of one patient was not recorded).
The mean age was 58.5 years (range, 11-94 years). Identification of larvae
revealed C. bezziana in 14 (87.5%) and C. megacephala in two (12.5%) patients.
The foot was affected in 15 (93. 7%) and the scalp in one patient. The immediate
predisposing factor for CM in dermatology patients was infected dermatitis. The
other relevant associated factors were: diabetes mellitus, psychiatric illness,
leprosy, and mental subnormality. Turpentine was a useful adjunct in the removal
of maggots manually. There were no side-effects to turpentine. In the in vitro
testing, turpentine was 100% effective in killing maggots. Some patients
required surgical removal under anesthesia. Indian beech and neem leaf extracts
were not effective against Chrysomya larvae in vitro. CONCLUSIONS: All cases of
CM were due to larvae of Chrysomya species. The commonest was C. bezziana. C.
megacephala larvae causing CM have been reported for the first time in Sri
Lanka. The foot was the site of predilection. Dermatitis, psychiatric illness,
leprosy, diabetes, and mental subnormality were some contributory factors.
Topically instilled mineral turpentine, followed by manual removal of maggots,
was effective in most cases. The plant extracts tested in vitro were
ineffective. As C. bezziana is an obligatory parasite capable of penetrating
deeply, the importance of preventive measures is emphasized.

PMID: 11044194 [PubMed - indexed for MEDLINE]

192: Arch Environ Contam Toxicol. 2000 Nov;39(4):486-93.

Effect of single and binary combinations of plant-derived molluscicides on
reproduction and survival of the snail Achatina fulica.

Rao IG, Singh DK.

Department of Zoology, DDU Gorakhpur University, Gorakhpur (U.P.) 273 009,

The effects of sublethal treatments (20% and 60% of LC(50)/24 h) with
plant-derived molluscicides on the reproduction of the giant African snail
Achatina fulica were studied. Azadirachta indica oil, Cedrus deodara oil, Allium
sativum bulb powder, and Nerium indicum bark powder singly and binary
combinations on reproduction and survival of A. fulica were investigated.
Repeated treatment occurred on day 0, day 15, and day 30. These plant-derived
molluscicides significantly reduced fecundity, egg viability, and survival of A.
fulica within 15 days. Discontinuation of the treatments after day 30 did not
lead to a recovery trend in the next 30 days. Day 0 sublethal treatment of all
the molluscicides caused a maximum reduction in protein, amino acid, DNA, RNA,
and phospholipid levels and simultaneous increase in lipid peroxidation in the
ovotestis of treated A. fulica. It is believed that sublethal exposure of these
molluscicides on snail reproduction is a complex process, involving more than
one factor in reducing the reproductive capacity of A. fulica.

PMID: 11031309 [PubMed - indexed for MEDLINE]

193: J Agric Food Chem. 2000 Aug;48(8):3666-72.

Effect of emulsion size and shelf life of azadirachtin A on the bioefficacy of
neem (Azadirachta indica A. Juss) emulsifiable concentrates.

Kumar L, Parmar BS.

Division of Agricultural Chemicals, Indian Agricultural Research Institute, New

In a study of 33 recipes of neem oil based emulsifiable concentrates, the
specific surface area of the emulsions and cream plus oil layer separation in
emulsions at 24 h revealed a correlation of -0.6874 between them and
correlations of -0.8940 and 0.6972, respectively, with bioefficacy (LC(50))
against the 3-day-old second-instar larvae of the Bihar hairy caterpillar,
Spilosoma obliqua Walker. Nearly 96-99% of azadirachtin A in emulsifiable
concentrates (aza-A content = 617.93-1149.65 ppm) degraded during the heat
stability test at 54 +/- 1 degrees C for 14 days with half-lives ranging between
1.84 and 4.53 days. The LC(50) values against S. obliqua were, however,
statistically at par in both the pre- and the post-heat-treated samples,
suggesting a similar effect of azadirachtin A and its degradation products on
the bioactivity. The half-life of azadirachtin A could be enhanced by storing
the concentrates at lower temperatures. A low pH of the formulation solvent did
not check the degradation of azadirachtin A, as reported with aqueous solutions
in the literature.

PMID: 10956167 [PubMed - indexed for MEDLINE]

194: J Chromatogr A. 2000 Jul 21;886(1-2):89-97.

Rapid and sensitive analysis of azadirachtin and related triterpenoids from Neem
(Azadirachta indica) by high-performance liquid chromatography-atmospheric
pressure chemical ionization mass spectrometry.

Schaaf O, Jarvis AP, van der Esch SA, Giagnacovo G, Oldham NJ.

Max-Planck-Institut fur Chemische Okologie, Jena, Germany.

Based on reversed-phase high-performance liquid chromatography (RP-HPLC) and
atmospheric pressure chemical ionization (APCI) mass spectrometry, a HPLC-MS
method was developed to permit the rapid qualitative and quantitative analysis
of azadirachtin and related tetranortriterpenoids from seeds and tissue cultures
of Neem (Azadirachta indica). APCI+ standard scanning mass spectra of the major
Neem triterpenoids were recorded and utilized to select suitable ions for
selected ion monitoring (SIM). Transitions for selective reaction monitoring
(SRM) were based on MS-MS experiments. Using SIM, major Neem triterpenoids were
detected in callus culture material and seed kernels of A. indica. The limit of
detection for azadirachtin in extract samples (approximately 1 ng ml(-1) or 10
pg in SIM mode) was determined to be (with respect to injected absolute amounts)
approximately 1000-times lower than values quoted in the literature for existing
HPLC methods (approximately 200 ng ml(-1) or 10 ng). In addition to high
sensitivity, the HPLC-MS method is able to tolerate minimal sample preparation
and purification, dramatically reducing total analysis time.

PMID: 10950279 [PubMed - indexed for MEDLINE]

195: J Ethnopharmacol. 2000 Aug;71(3):377-82.

Anti-microbial activity of a new vaginal contraceptive NIM-76 from neem oil
(Azadirachta indica).

SaiRam M, Ilavazhagan G, Sharma SK, Dhanraj SA, Suresh B, Parida MM, Jana AM,
Devendra K, Selvamurthy W.

Defence Institute of Physiology and Allied Sciences, Ministry of Defence,
Timarpur, -1 10054, Delhi, India.

Efficacy of NIM-76, a spermicidal fraction from neem oil, was investigated for
its antimicrobial action against certain bacteria, fungi and Polio virus as
compared to whole neem oil. The NIM-76 preparation showed stronger
anti-microbial activity than the whole neem oil. It inhibited growth of various
pathogens tested including Escherichia coli and Kleibsiella pneumoniae which
were not affected by the whole neem oil. NIM-76 also exhibited antifungal
activity against Candida albicans and antiviral activity against Polio virus
replication in vero cell lines. It also protected mice from systemic candidiasis
as revealed by enhanced % survival and reduced colony forming units of C.
albicans in various tissues. This shows that NIM-76 has a potent broad spectrum
anti-microbial activity.

PMID: 10940573 [PubMed - indexed for MEDLINE]

196: J Exp Bot. 2000 Mar;51(344):635-43.

A study of water relations in neem (Azadirachta indica) seed that is
characterized by complex storage behaviour.

Sacande M, Buitink J, Hoekstra FA.

Centre National de Semences Forestieres (CNSF), Ouagadougou, Burkina Faso.
[email protected]

Neem (Azadirachta indica) seed is reputed to have limited tolerance to
desiccation, to be sensitive to chilling and imbibitional stress, and to display
intermediate storage behaviour. To understand this behaviour the properties of
water in seed tissues were studied. Water sorption isotherms showed that at
similar relative humidity (RH), the water content was consistently higher in
axes than in cotyledons, mainly due to the elevated lipid content (51%) in the
cotyledons. Using differential scanning calorimetry, melting transitions of
water were observed at water contents higher than 0.14 g H2O g-1 DW in the
cotyledons and 0.23 g H2O g-1 DW in the axes. Beside melting transitions of
lipid, as verified by infrared spectroscopy, changes in heat capacity were
observed which shifted with water content, indicative of glass-to-liquid
transitions. State diagrams are given on the basis of the water content of seed
tissues, and also on the basis of the RH at 20 degrees C. Longevity was
considerably improved, and the sensitivity to chilling/subzero temperatures was
reduced when axis and cotyledons were dehydrated to moisture contents < or = of
approximately 0.05 g H2O g-1 DW. However, longevity during storage at very low
water contents was limited. A possible mechanism for the loss of sensitivity to
chilling/subzero temperatures at low water contents is discussed. The results
suggest that dry neem seeds in the glassy state have great potential for
extended storability, also at subzero temperatures.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10938819 [PubMed - indexed for MEDLINE]

197: J Commun Dis. 1999 Dec;31(4):241-5.

Field evaluation of herbal mosquito repellents.

Das NG, Nath DR, Baruah I, Talukdar PK, Das SC.

Repellent properties of Zanthoxylum armatum DC. Syn. Z. alatum Roxb. (Timur),
Curcuma aromatica (Jungli haldi) and Azadirachta indica (Neem) oils were
evaluated against mosquitoes in mustard (Brassica sp.) and coconut (Cocos sp.)
oil base and compared with synthetic repellent. Dimethyl phthalate (DMP) as
standard. Timur and jungli haldi afforded better protection in the both the base
at all the concentrations. Tepellents in mustard oil gave longer protection time
than those in coconut oil. At 0.57 mg/cm2 concentration timur oil gave
significantly higher protection both in mustard (445 min) as well as coconut oil
(404 min) than the other repellents and DMP.

Publication Types:
Clinical Trial
Comparative Study

PMID: 10937301 [PubMed - indexed for MEDLINE]

198: Indian J Physiol Pharmacol. 2000 Jan;44(1):69-74.

A study of hypoglycaemic effects of Azadirachta indica (Neem) in normaland
alloxan diabetic rabbits.

Khosla P, Bhanwra S, Singh J, Seth S, Srivastava RK.

Hypoglycaemic effect was observed with Azadirachta indica when given as a leaf
extract and seed oil, in normal as well as diabetic rabbits. The effect,
however, was more pronounced in diabetic animals in which administration for 4
weeks after alloxan induced diabetes, significantly reduced blood glucose
levels. Hypoglycaemic effect was comparable to that of glibenclamide.
Pretreatment with A. indica leaf extract or seed oil administration, started 2
weeks prior to alloxan, partially prevented the rise in blood glucose levels as
compared to control diabetic animals. The data suggests that A. indica could be
of benefit in diabetes mellitus in controlling the blood sugar or may also be
helpful in preventing or delaying the onset of the disease.

PMID: 10919098 [PubMed - indexed for MEDLINE]

199: Indian J Physiol Pharmacol. 2000 Jan;44(1):64-8.

Effect of Azadirachta indica (Neem) leaf aqueous extract on paracetamol-induced
liver damage in rats.

Bhanwra S, Singh J, Khosla P.

Department of Pharmacology, Pt. B.D. Sharma P.G.I.M.S., Rohtak.

The effect of aqueous leaf extract of Azadirachta indica (A. indica) was
evaluated in paracetamol induced hepatotoxicity in rats. Liver necrosis was
produced by administering single dose of paracetamol (2 g/kg, p.o.). The liver
damage was evidenced by elevated levels of serum aspartate aminotransferase
(AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (gamma-GT)
and by histopathological observations of liver sections. Aqueous A. indica leaf
extract (500 mg/kg, p.o.) significantly (P < 0.01) reduced these elevated levels
of AST, ALT and gamma-GT. Paracetamol induced liver necrosis was also found to
be reduced as observed macroscopically and histologically.

PMID: 10919097 [PubMed - indexed for MEDLINE]

200: Indian J Exp Biol. 1999 Dec;37(12):1251-4.

Effect of Azadirachta indica leaves on rat spermatozoa.

Aladakatti RH, Ahamed RN.

Department of Studies & Research in Zoology, Karnatak University, Dharwad,

Histochemical studies and SEM observations on the morphological changes in the
head of the spermatozoa in general, and the acrosome in particular, in A. indica
treated rats are reported. In the treated rats change in the shape and size of
the sperm head, with a dorso-ventral constriction of the middle region of the
sperm head i.e., between the anterior and posterior regions was observed. It was
rather difficult to differentiate the outer acrosomal and outer plasma
membranes. A decrease in the perforatorium or sub-acrosomal material, post
nuclear cap and the nuclear material near the basal plate at the base of the
sperm head were also observed. The results suggest that the effects are probably
due to androgen deficiency and a general disturbance in carbohydrates or
polysaccharides located in the sperm head, caused by the antiandrogenic property
of the leaves of A. indica.

PMID: 10865894 [PubMed - indexed for MEDLINE]

201: Indian J Dent Res. 1999 Jan-Mar;10(1):23-6.

The antimicrobial effects of extracts of Azadirachta indica (Neem) and Salvadora
persica (Arak) chewing sticks.

Almas K.

Department of Preventive Dental Sciences, College of Dentistry, Riyadh, Kingdom
of Saudi Arabia. [email protected]

Chewing sticks (Miswak) is most commonly used int he Middle East and Indian
Subcontinent Salvadora persica (Arak) and Azadirachta indica (Neem) are commonly
used as oral hygiene tools in different parts of the world, Several studies have
demonstrated the anti-plaque anticarious and antibacterial effect of these
sticks. The aim of this study was to compare the effectiveness of antimicrobial
activity of Neem and Arak chewing stick's aqueous extracts at various
concentrations. The microbial inhibition was measured using blood agar and ditch
plate method up to 48 hous. The pH of Neem extract was 6.1 and of Arak was 4.9
Data suggested that both chewing stick extracts are effective at 50%
concentration on strept mutans and Strept faecalis. Arak extract was more
effective at lower concentrations for Strept faecalis. The effect may be due to
the difference of their chemical composition and variability in their PH.
Further research is needed to extrapolate other plants used for oral hygiene.
Chewing sticks are recommended as oral hygiene tools for health promotion in
developing countries.

PMID: 10865390 [PubMed - indexed for MEDLINE]

202: Phytother Res. 2000 Jun;14(4):291-3.

Garlic and neem leaf extracts enhance hepatic glutathione and glutathione
dependent enzymes during N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced
gastric carcinogenesis in rats.

Arivazhagan S, Balasenthil S, Nagini S.

Department of Biochemistry, Annamalai University, Annamalainagar 608 002, Tamil
Nadu, India.

The protective effect of garlic (Allium sativum L.) and neem leaf (Azadirachta
indica A. Juss.) was investigated on hepatic lipid peroxidation and antioxidant
status during N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric
carcinogenesis in male Wistar rats. Enhanced lipid peroxidation in the liver of
tumour-bearing animals was accompanied by significant decreases in the
activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST),
gamma-glutamyl transpeptidase (GGT) and reduced glutathione (GSH) levels.
Administration of garlic and neem leaf extracts significantly lowered lipid
peroxidation and enhanced the hepatic levels of glutathione and glutathione
dependent enzymes. We speculate that garlic and neem leaf significantly alter
cancer development at extrahepatic sites by influencing hepatic
biotransformation enzymes and antioxidants. Copyright 2000 John Wiley & Sons,

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10861977 [PubMed - indexed for MEDLINE]

203: Fitoterapia. 2000 Jun;71(3):317-20.

Antifungal activity of some tetranortriterpenoids.

Govindachari TR, Suresh G, Gopalakrishnan G, Masilamani S, Banumathi B.

Centre for Agrochemical Research, SPIC Science Foundation, 111, Mount Road, 600
032, Madras, India. [email protected]

Natural tetranortriterpenoids such as cedrelone from Toona ciliata, azadiradione
from Azadirachta indica, limonin, limonol and nomilinic acid from Citrus medica,
along with some cedrelone derivatives were tested for their antifungal activity
against Puccinia arachidis, a groundnut rust pathogen. Results show that
cedrelone was the most effective in reducing rust pustule emergence. Replacement
of functional groups or modification of the A or the B ring in cedrelone reduced
the effectiveness indicating the importance of specific structural features for

PMID: 10844171 [PubMed - indexed for MEDLINE]

204: Prev Vet Med. 2000 Jun 12;45(3-4):201-20.

Medicinal plants used for dogs in Trinidad and Tobago.

Lans C, Harper T, Georges K, Bridgewater E.

Faculty of Medical Sciences, School of Veterinary Medicine, University of the
West Indies, Mt. Hope, Trinidad and Tobago. [email protected]

This paper documents ethnoveterinary medicines used to treat dogs in Trinidad
and Tobago. In 1995, a 4-stage process was used to conduct the research and
document the ethnoveterinary practices. Twenty-eight ethnoveterinary respondents
were identified using the school-essay method, which is a modified rapid rural
appraisal (RRA) technique. Semi-structured interviews were held with these
respondents as well as with 30 veterinarians, 27 extension officers and 19
animal-health assistants and/or agricultural officers, and the seven key
respondents that they identified. The final step involved hosting four
participatory workshops with 55 of the respondents interviewed to discuss the
ethnoveterinary data generated from the interviews and to determine dosages for
some of the plants mentioned. Supplementary interviews were conducted in 1997
and 1998.Seeds of Carica papaya, and leaves of Cassia alata, Azadirachta indica,
Gossypium spp., Cajanus cajan and Chenopodium ambrosiodes are used as
anthelmintics. The anthelmintics Gossypium spp. and Chenopodium ambrosiodes are
the most frequently used species. Crescentia cujete pulp, Musa spp. stem
exudate, the inside of the pods of Bixa orellana, leaves of Cordia curassavica
and Eclipta alba plant tops are used for skin diseases. Musa spp. stem exudate,
seeds of Manilkara zapota, Pouteria sapota and Mammea americana and leaves of
Cordia curassavica, Scoparia dulcis and Nicotiana tabacum are used to control
ectoparasites. Dogs are groomed with the leaves of Cordia curassavica, Bambusa
vulgaris and Scoparia dulcis. Psidium guajava buds and leaves and the bark of
Anacardium occidentale are used for diarrhoea. Owners attempt to achieve milk
let-down with a decoction of the leaves of Stachytarpheta jamaicensis. The plant
uses parallel those practised in human folk medicine in other Caribbean
countries and in other tropical countries.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10821961 [PubMed - indexed for MEDLINE]

205: J Commun Dis. 1999 Jun;31(2):79-90.

'In vitro' antiviral activity of neem (Azadirachta indica. A. Juss) leaf extract
against group B coxsackieviruses.

Badam L, Joshi SP, Bedekar SS.

National Institute of Virology, Pune, India.

The antiviral and virucidal effect of methanolic extract fraction of leaves of
neem (Azadirachta indica A. Juss) (NCL-11) was studied regarding its activity
and possible mechanism of action against Coxsackie B group of viruses. NCL-11
inhibited plaque formation in 6 antigenic types of Coxsackie virus B at a
concentration of 1000 micrograms/ml at 96 hrs. 'in vitro'. Additionally virus
inactivation, yield reduction and effect of time of addition assays suggested
that NCL-11 was most effective against coxsackie virus B-4 as a virucidal agent
besides interfering at an early event of its replicative cycle. The evidence
suggested that presence of a battery of compounds besides flavonoids,
triterpenoids and their glycosides in NCL-11 have antiviral action for coxsackie
B group of viruses 'in vitro.' The minimal inhibitory concentrations were not
toxic to Vero (African green monkey kidney), cells; subtoxic concentration was
8,000 micrograms/ml and cytotoxic concentration 10,000 micrograms/ml, which was
confirmed by trypan blue dye exclusion test.

PMID: 10810594 [PubMed - indexed for MEDLINE]

206: J Egypt Soc Parasitol. 2000 Apr;30(1):221-31.

Toxicity of a Neem (Azadirachta indica) insecticide to certain aquatic

el-Shazly MM, el-Sharnoubi ED.

Department of Entomology, Faculty of Science, Cairo University, Giza, Egypt.

Neem based insecticides are likely to show a large increase in use in the near
future. In the present work, the toxicity of a neem insecticide, Neem-Azal-T/S,
was tested against the mosquito larvae, as well as against certain non target
organisms occurring in a polluted pond and a shallow stream, located in a
cultivated area in Giza, Egypt. Samples of water containing the experimental
animals were collected from this area, and toxicity tests were conducted in the
laboratory by exposing them to a series of concentrations of the botanical
insecticide, using the water of the pond and stream at room temperature (28-31
degrees C). The compound was more or less toxic to all the tested species. The
LC50S and mortality rates were determined. The order of tolerance of the
organisms to different concentrations of the insecticide was: larvae of Bufo
regularis (Amphibia) > Aedes caspius. (Insecta) > Gambusia affinis (Poeciliidae)
> Cyclops sp. > Daphnia magna (Crustacea). At a concentration of 20 ppm, all the
tadpoles died within 9 days, while all other individuals died within 5 to 8 days
after exposure to a concentration of 10 ppm of Neem Azal insecticide.

PMID: 10786033 [PubMed - indexed for MEDLINE]

207: Indian J Exp Biol. 1999 Nov;37(11):1097-100.

Neem (Azadirachta indica) extract as an antibacterial agent against fish
pathogenic bacteria.

Das BK, Mukherjee SC, Sahu BB, Murjani G.

Aquatic Animal Health Division, Central Institute of Freshwater Aquaculture,
Bhubaneswar, India.

Aquaneem, an emulsified product prepared from the neem (A. indica) kernel was
tested against four pathogenic bacteria of fish (i.e. Aeromonas hydrophila,
Pseudomonas fluorescens, Escherichia coli and Myxobacteria spp.) to test its
efficacy as an antibacterial agent. Growth inhibitory property of the product at
10, 15 and 20 ppm has been noticed and recorded. The percentage reduction of
bacterial cell population was noted to be maximum on 9th day at 20 ppm
concentration (i.e. 70.14%, 74.15% and 61.75% for A. hydrophila, P. fluorescens
and E. coli respectively) with the only exception of myxobacteria which showed
maximum reduction percentage (63.90%) on 15th day. Among all the bacteria tested
A. hydrophila, P. fluorescens and Myxobacteria spp. exhibited maximum
sensitivity to Aquaneem in terms of percentage reduction of bacterial cell
population in comparison to E. coli.

PMID: 10783742 [PubMed - indexed for MEDLINE]

208: J Stored Prod Res. 2000 Jul 1;36(3):215-222.

Potential of combining neem (Azadirachta indica A. Juss) seed oil with varietal
resistance for the management of the cowpea bruchid, Callosobruchus maculatus

Lale NE, Mustapha A.

Department of Crop Science, Faculty of Agriculture, University of Maiduguri, P.
M. B. 1069, Maiduguri, Nigeria

The efficacy of different rates (25, 50, 75 and 100 mg/5 g seed) of application
of neem (Azadirachta indica) seed oil (NSO) was assessed on four cowpea
varieties (Kanannado, IT89KD-391, Borno brown and IT89KD-374) with differing
susceptibilities to Callosobruchus maculatus. The different rates of NSO
significantly interacted with cowpea varietal resistance and reduced oviposition
and percentage adult emergence of C. maculatus. The interaction of the
strategies also significantly reduced percentage of cowpea seeds infested by C.
maculatus. Treatment of seeds with NSO at the rates of 50 mg/5 g and 75 or 100
mg/5 g reduced seed damage from over 25% in controls to less than 10% and less
than 5%, respectively, in all varieties.

PMID: 10758260 [PubMed - as supplied by publisher]

209: Phytochemistry. 2000 Feb;53(3):371-6.

Two insecticidal tetranortriterpenoids from Azadirachta indica.

Siddiqui BS, Afshan F, Ghiasuddin, Faizi S, Naqvi SN, Tariq RM.

H.E.J. Research Institute of Chemistry, University of Karachi, Pakistan.
[email protected]

Two new triterpenoids, 6 alpha-O-acetyl-7-deacetylnimocinol
[24,25,26,27-tetra-norapotirucalla-(apoeupha)-6 alpha-acetoxy-7
alpha-hydroxy-1,14,20,22-tetraen-21,23-epoxy-3-one] (1) and meliacinol
[24,25,26,27-tetranorapotirucalla-(apoeupha)-1 alpha-trimethylacryloxy-21,23-6
alpha,28-diepoxy-16-oxo-17-oxa-14,20,22-trien-3 alpha,7 alpha-diol] (2) were
isolated from the methanolic extract of the fresh leaves of Azadirachta indica
(neem). Their structures have been elucidated through spectral studies,
including 2D-NMR (COSY-45, NOESY, HMQC and HMBC). The bioactivity of these as
well as of nimocinol, reported earlier from the same source, is reported. The
first compound and nimocinol showed toxicity on fourth instar larvae of
mosquitoes (Aedes aegypti) with LC50 values of 21 and 83 ppm, respectively. The
second compound had no effect upto 100 ppm.

PMID: 10703059 [PubMed - indexed for MEDLINE]

210: J Control Release. 2000 Jan 3;63(1-2):97-105.

Glutaraldehyde crosslinked sodium alginate beads containing liquid pesticide for
soil application.

Kulkarni AR, Soppimath KS, Aminabhavi TM, Dave AM, Mehta MH.

Department of Chemistry, Karnatak University, Dharwad, India.

This paper presents experimental results on the successful encapsulation of a
natural liquid pesticide 'neem (Azadirachta Indica A. Juss.) seed oil' hereafter
designated as NSO, using sodium alginate (Na-Alg) as a controlled release (CR)
polymer after crosslinking with glutaraldehyde (GA). The NSO-containing beads
have been prepared by changing the experimental variables such as the extent of
crosslinking and the amount of loading in order to optimize the process
variables. The absence of chemical interactions between active ingredients and
polymer as well as crosslinking agent was confirmed by FTIR spectral
measurements. The SEM data indicated that the structure of the walls of the
beads are smooth and nonporous. The swelling results indicated that swelling of
the polymeric beads decreases with increasing exposure time to the crosslinking
agent. However, no significant variation in swelling was observed with different
amounts of NSO loading. In order to understand the crosslinkability and its
effect on the NSO release patterns of the beads, an attempt was made to
calculate the molar mass between crosslinks using the Flory-Rehner equation. The
release data have been fitted to an empirical equation to estimate the kinetic

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10640583 [PubMed - indexed for MEDLINE]

211: Arch Environ Contam Toxicol. 2000 Feb;38(2):182-90.

Effect of different combinations of MGK-264 or piperonyl butoxide with
plant-derived molluscicides on snail reproduction.

Singh K, Singh DK.

Department of Zoology, DDU Gorakhpur University, Gorakhpur (U.P.) 273 009,

Effect of sublethal treatment (20% and 60% of LC(50)/24 h) of plant-derived
molluscicides, viz. Polianthes tuberosa, Trachyspermum ammi, Allium sativum
powder; Azadirachta indica oil; oleoresin of Zingiber officinale; and their
active molluscicidal component in combination (1:5) with MGK-264 or piperonyl
butoxide on the reproduction of snail Lymnaea acuminata have been studied. It
was observed that the combination of plant derived molluscicide and their active
molluscicidal components, viz. tigogenin, hecogenin, azadirachtin, allicin,
thymol, and [6]-gingerol combination with MGK-264 or piperonyl butoxide caused a
significant reduction in fecundity, hatchability, and survival of young snails.
Withdrawal of snails to fresh water after the above treatment caused a
significant recovery in the fecundity of L. acuminata.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10629280 [PubMed - indexed for MEDLINE]

212: J Ethnopharmacol. 1999 Nov 1;67(2):189-95.

Chemopreventive potential of neem (Azadirachta indica) on
7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch

Balasenthil S, Arivazhagan S, Ramachandran CR, Ramachandran V, Nagini S.

Department of Biochemistry, Faculty of Science, Annamalai University, Tamil
Nadu, India.

The inhibitory effect of the aqueous extract of neem (Azadirachta indica A.
Juss.) on 7,12-dimethylbenz[a]anthracene (DMBA) induced buccal pouch
carcinogenesis was investigated in Syrian male hamsters. All hamsters painted on
their buccal pouch with DMBA for 14 weeks developed squamous cell carcinoma.
Administration of neem leaf extract effectively suppressed oral carcinogenesis
initiated with DMBA as revealed by the reduced incidence of neoplasms. Lipid
peroxidation, glutathione (GSH) content and the activities of glutathione
peroxidase (GPx), glutathione S-transferase (GST) and gammaglutamyl
transpeptidase (GGT) were used to biomonitor the chemopreventive potential of
neem. Lipid peroxidation was found to be significantly decreased, whereas GSH,
GPx, GST and GGT were elevated in the oral mucosa of tumour bearing animals. Our
data suggest that neem may exert its chemopreventive effects in the oral mucosa
by modulation of lipid peroxidation, antioxidants and detoxification systems.

PMID: 10619383 [PubMed - indexed for MEDLINE]

213: J Ethnopharmacol. 1999 Nov 30;67(3):373-6.

Possible mechanism of antihyperglycemic effect of Azadirachta indica leaf
extract: part V.

Chattopadhyay RR.

Biometry Research Unit, Indian Statistical Institute, Calcutta.

Effect of Azadirachta indica leaf extract on serotonin inhibition in glucose
mediated insulin release in rat pancreas was studied in vitro to elucidate the
possible mechanism of antihyperglycemic effect of A. indica leaf extract. A.
indica leaf extract blocks significantly (P < 0.05) the inhibitory effect of
serotonin on insulin secretion mediated by glucose.

Publication Types:
In Vitro

PMID: 10617075 [PubMed - indexed for MEDLINE]

214: J Ethnopharmacol. 1999 Nov 30;67(3):367-72.

A comparative evaluation of some blood sugar lowering agents of plant origin.

Chattopadhyay RR.

Biometry Research Unit, Indian Statistical Institute, Calcutta.

A comparison of blood sugar lowering activity of four important medicinal plants
(Azadirachta indica, Gymnema sylvestre, Catharanthus roseus and Ocimum sanctum)
were carried out against normal and streptozotocin-induced diabetic rat models.
The plant extracts decreased the blood sugar level in varying degrees. Blood
sugar lowering unit (BLU) of activity of each leaf extract and tolbutamide was
calculated by ED50 values. Statistical analysis revealed significant (P < 0.05)
variation among the treatments as well as doses with regard to their blood sugar
lowering capacity. A. indica leaf extract was found to have the most potent
blood sugar-lowering activity followed by C. roseus, G. sylvestre and O.

Publication Types:
Comparative Study

PMID: 10617074 [PubMed - indexed for MEDLINE]

215: J Ethnopharmacol. 1999 Nov 30;67(3):287-96.

Early post implantation contraceptive effects of a purified fraction of neem
(Azadirachta indica) seeds, given orally in rats: possible mechanisms involved.

Mukherjee S, Garg S, Talwar GP.

National Institute of Immunology, and International Center for Genetic
Engineering and Biotechnology, New Delhi, India. [email protected]

Neem seed and leaf extracts have immunomodulators that induce cellular immune
reactions. These aspects of neem were exploited in earlier studies, where the
oral administration of the neem seed extracts in rodents and primates could
completely abrogate pregnancy at an early post implantation stage. Complete
restoration of fertility was observed in the animals treated in the subsequent
cycles. For the purpose of using neem as a long term contraceptive, an activity
guided fractionation, followed by identification and characterization of the
biologically active fraction from neem seeds was carried out. Sequentially
extracted fractions of neem seeds were tested orally at an early post
implantation stage in rats. The hexane extract of the neem seeds was found to be
biologically active and was the precursor for the final active fraction. The
active fraction, identified as a mixture of six components, could completely
abrogate pregnancy in rodents up to a concentration of 10%. No apparent toxic
effects could be seen following treatment with the fraction. The treatment with
the active fraction caused a specific activation of T lymphocyte cells of CD8+
subtype as well as phagocytic cells followed by elevation in cytokines
gamma-interferon and TNF. The results of the present study show that a pure
active fraction of neem seeds could be obtained for the purpose of early post
implantation contraception when given orally, and its mechanism of action seems
to be by activating cell mediated immune reactions.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10617063 [PubMed - indexed for MEDLINE]

216: Fortschr Chem Org Naturst. 1999;78:47-149.

Chemistry of the neem tree (Azadirachta indica A. Juss.).

Akhila A, Rani K.

Phytochemical Technology Division, Central Institute of Medicinal and Aromatic
Plants, Lucknow, India.

Publication Types:

PMID: 10592761 [PubMed - indexed for MEDLINE]

217: Onderstepoort J Vet Res. 1999 Mar;66(1):59-62.

Effect of an aqueous extract of Azadirachta indica on the immune response in

Njiro SM, Kofi-Tsekpo MW.

Department of Veterinary Pathology and Microbiology, University of Nairobi,
Kabete, Kenya.

Because of the very wide spectrum of infectious and non-infectious diseases for
which preparations from Azadirachta indica are said to be efficacious, it was
suspected that a general immunopotentiating ability could be part of the
mechanisms by which it ameliorates so many disease conditions. Using the
haemolytic plaque technique, an aqueous extract of Azadirachta indica stem bark
was shown to enhance the immune response of BALB/C mice to sheep red blood cells
in vivo.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10396765 [PubMed - indexed for MEDLINE]

218: Naturwissenschaften. 1999 Nov;86(11):538-9.

Coating of prilled urea with neem (Azadirachta indica juss) oil for efficient
nitrogen use in rice

Prasad R, Singh S, Saxena VS, Devkumar C.

Indian Agricultural Research Institute, New Delhi 110012, India.

A field study made with rice at the Indian Agricultural Research Institute, New
Delhi, showed that coating urea with neem oil, neem cake or neem oil
microemulsion improved rice growth and resulted in more grain and straw than did
commercial prilled urea.

PMID: 10551949 [PubMed - as supplied by publisher]

219: J Enzyme Inhib. 1998;14(1):85-96.

Isolation of antioxidant principle from Azadirachta seed kernels: determination
of its role on plant lipoxygenases.

Rao AD, Devi KN, Thyagaraju K.

Department of Biochemistry, Sri Venkateswara University, Tirupati, India.

An antioxidant principle was isolated from Azadirachta indica seed using high
pressure liquid chromatography with a hydrophobic reverse-phase chromatography
column. The eluted molecule had lambdamax at 224 and 272 nm and was a potent
inhibitor of plant lipoxygenases. In in vivo studies of horsegram during
germination, low levels of lipoxygenase activity and lipid peroxides were found
upon treatment with the Azadirachta extract. The antioxidant property of
Azadirachta indica has not been previously reported.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10520761 [PubMed - indexed for MEDLINE]

220: Phytother Res. 1999 Aug;13(5):388-92.

Toxic and growth retarding effects of three plant extracts on Culex pipiens
larvae (Diptera: Culicidae).

El Hag EA, El Nadi AH, Zaitoon AA.

College of Agriculture and Veterinary Medicine, King Saud University, Gassim
Branch, PO Box 1482, Buraydah, Saudi Arabia.

The toxic and/or development retarding effects on Culex pipiens mosquito larvae
by methanol and ether extracts of Azadirachta indica, Rhazya stricta and
Syzygium aromaticum were investigated separately. All were found to show
biological activity, however, the methanol extracts showed the most profound
effects. R. stricta showed marked acute (2 d) and chronic (10 d) toxic effects,
having an LC(50) and 95% CL of 251(209-326) and 140(110-178); 467(416-699) and
211(198-421) ppm, for the methanol and ether extracts, respectively. Only 3.3%
of the larvae pupated and no adults emerged even at the lowest concentration
(200 ppm) of methanol extract. Both A. indica extracts were toxic to C. pipiens
larvae but at higher concentrations, showing an acute and chronic LC(50) and 95%
CL of 824(692-980) and 265(111-481); 1620(1380-1892) and 675(514-887) ppm for
the methanol and ether extracts, respectively. The methanol extracts of A.
indica, at concentrations above 800 ppm, reduced pupation to 3.3% and completely
inhibited adult emergence. Both extracts of S. aromaticum were less toxic to the
larvae, however their influence on development was remarkable, causing complete
inhibition of adult emergence at 200 and 600 ppm concentrations of the methanol
and ether extracts, respectively. Future application of these extracts to larval
habitats may lead to promising results in mosquito management programmes.
Copyright 1999 John Wiley & Sons, Ltd.

PMID: 10441777 [PubMed - indexed for MEDLINE]

221: Plant Foods Hum Nutr. 1998;52(4):293-8.

Morphological and oil content variation in seeds of Azadirachta indica A. Juss.
(Neem) from northern and western provenances of India.

Kaura SK, Gupta SK, Chowdhury JB.

Department of Genetics, CCS Haryana Agricultural University, Hisar, India.

Seed morphology (seed length and 20 seed weight) and oil content was studied in
Azadirachta indica A. Juss. (Neem) of five provenances of northern and western
India. Trees with wide ranges of girths were considered for study. Maximum
average oil content was observed in trees from Hisar provenance. Seed oil
content in most of the provenances was not consistently and significantly
correlated with morphological parameters of seeds. Age of the tree had no
significant effect on the oil yield.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10426116 [PubMed - indexed for MEDLINE]

222: J Nat Prod. 1999 Jul;62(7):1022-4.

Two novel azadirachtin derivatives from azadirachta indica

Luo X, Ma Y, Wu S, Wu D.

Laboratory of Phytochemistry, Kunming Institute of Botany, Academia Sinica,
Kunming 650204 Yunnan, People's Republic of China.

Two novel compounds, the first 29-oxymethylene azadirachtin analogue,
29-oxymethylene-11- demethoxycarbonyl-11alpha-hydroxyazadirachtin (azadirachtin
M) (1) and 22, 23-dihydro-23alpha-hydroxy-3-tigloyl-11-deoxyazadirachtinin
(azadirachtin N) (2), together with known compound 11-epi-azadirachtin H were
isolated from a methanolic extract of the seed kernels of Azadirachta indica.
The structures of 1 and 2 were elucidated on the basis of spectral methods.

PMID: 10425132 [PubMed - as supplied by publisher]

223: J Nat Prod. 1999 Jul;62(7):1006-9.

Triterpenoids of the fruit coats of azadirachta indica

Siddiqui BS, Ghiasuddin G, Faizi S, Rasheed M.

H.E.J. Research Institute of Chemistry, University of Karachi, Karachi-75270,

Three new triterpenoids, azadironolide [24,25,26,
20(22)-trien-3,21-dione] (1), isoazadironolide [24,25,26,
20(22)-trien-3,23-dione] (2), and azadiradionolide [24,25,26,
16,21-trione] (3), were isolated from the fresh fruit coats of Azadirachta
indica. Their structures have been elucidated through spectral analysis.

PMID: 10425127 [PubMed - as supplied by publisher]

224: J Am Mosq Control Assoc. 1999 Jun;15(2):133-52.

Activity and biological effects of neem products against arthropods of medical
and veterinary importance.

Mulla MS, Su T.

Department of Entomology, University of California, Riverside 92521-0314, USA.

Botanical insecticides are relatively safe and degradable, and are readily
available sources of biopesticides. The most prominent phytochemical pesticides
in recent years are those derived from neem trees, which have been studied
extensively in the fields of entomology and phytochemistry, and have uses for
medicinal and cosmetic purposes. The neem products have been obtained from
several species of neem trees in the family Meliaceae. Six species in this
family have been the subject of botanical pesticide research. They are
Azadirachta indica A. Juss, Azadirachta excelsa Jack, Azadirachta siamens
Valeton, Melia azedarach L., Melia toosendan Sieb. and Zucc., and Melia
volkensii Gurke. The Meliaceae, especially A. indica (Indian neem tree),
contains at least 35 biologically active principles. Azadirachtin is the
predominant insecticidal active ingredient in the seed, leaves, and other parts
of the neem tree. Azadirachtin and other compounds in neem products exhibit
various modes of action against insects such as antifeedancy, growth regulation,
fecundity suppression and sterilization, oviposition repellency or attractancy,
changes in biological fitness, and blocking development of vector-borne
pathogens. Some of these bioactivity parameters of neem products have been
investigated at least in some species of insects of medical and veterinary
importance, such as mosquitoes, flies, triatomines, cockroaches, fleas, lice,
and others. Here we review, synthesize, and analyze published information on the
activity, modes of action, and other biological effects of neem products against
arthropods of medical and veterinary importance. The amount of information on
the activity, use, and application of neem products for the control of disease
vectors and human and animal pests is limited. Additional research is needed to
determine the potential usefulness of neem products in vector control programs.

Publication Types:

PMID: 10412110 [PubMed - indexed for MEDLINE]

225: Br Poult Sci. 1999 Mar;40(1):77-83.

Performance of broiler chicks fed on diets containing urea ammoniated neem
(Azadirachta indica) kernel cake.

Nagalakshmi D, Sastry VR, Katiyar RC, Agrawal DK, Verma SV.

Division of Animal Nutrition, Indian Veterinary Research Institute, Izatnagar.

1. The performance, nutrient utilisation, blood profile, carcase composition,
gross pathology and sensory evaluation of meat from broiler chicks fed from 3 to
42 d on diets containing urea ammoniated neem (Azadirachta indica, A.juss)
kernel cake (NKC) as a protein supplement to replace peanut meal (PNM), were
evaluated. NKC was ammoniated with urea at 15 (UANKC 1) or 25 g (UANKC 2)/kg and
incorporated into the test diets to replace either half (134.5 g/kg (L-UANKC 1)
and 127.5 g/kg (L-UANKC 2), respectively) or all (269, g/kg (H-UANKC 1) and
255.0 g/kg (H-UANKC 2), respectively) of the nitrogen provided by the PNM. 2.
The growth, food intake and efficiency of nutrient utilisation of the birds were
comparable between the reference and L-UANKC 1 and 2 diets but were depressed on
the other UANKC diets. 3. The retention of dry matter (DM), crude fibre (CF),
nitrogen-free extract, total carbohydrate, gross energy, acid detergent fibre,
calcium and phosphorus were similar among groups, except lower DM and higher CF
and phosphorus retentions were noted in chicks fed on the H-UANKC 1, H-UANKC 2
and L-UANKC 2 diets. All the chicks were in positive nitrogen balance and
percentage nitrogen retention did not differ between the reference and test
diets. 4. Haemoglobin, total erythrocyte count and aspartate amino transferase
activity were unaffected by diet, but total leucocyte count was higher in chicks
fed on the H-UANKC 1 and 2 diets and alanine amino transferase activities were
lower in chicks fed on the test diets. Blood urea increased as the amount of
urea in the diets increased. 5. Most of the physico-chemical carcase
characteristics from birds fed on the L-UANKC 2 were comparable to those from
birds fed on the reference diet. No bitter taste was noticed in cooked meat from
any diet by the sensory panel. 6. Incorporation of L-UANKC 2 was economical and
responses were comparable to those observed on the reference diet. 7. It was
concluded that NKC detoxified with 25 g urea/kg can economically and
successfully replace half the nitrogen of PNM in broiler diets thereby
mitigating the chronic shortage of costly oil cakes in developing countries.

Publication Types:
Comparative Study

PMID: 10405039 [PubMed - indexed for MEDLINE]

226: J Ethnopharmacol. 1999 Mar;64(3):227-33.

Antiplasmodial activity of selected Sudanese medicinal plants with emphasis on
Maytenus senegalensis (Lam.) Exell.

El Tahir A, Satti GM, Khalid SA.

Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan.

The antiplasmodial activity of plant extracts related to four families was
tested on chloroquine sensitive strain 3D7 and chloroquine resistant strain Dd2
of Plasmodium falciparum. The methanolic extract of Harrisonia abyssinica
(Simaroubaceae) inhibited Dd2 with IC50 value of 4.7 microg/ml, while in 3D7,
the IC50 value was 10 microg/ml. Most of the plants from the family Meliaceae
showed highly potent antiplasmodial activity against the two tested strains.
Khaya senegalensis, Azadirachta indica and Trichilia emetica showed IC50 values
less than 5 microg/ml. The methanolic extract of Annona squamosa (Annonaceae)
leaves showed high antiplasmodial activity with IC50 values of 2 and 30
microg/ml on 3D7 and Dd2, respectively. While stem bark showed moderate activity
with IC50 values of 8.5 and 120 microg/ml on Dd2. Maytenus senegalensis
(Celastraceae) possessed IC50 values of 3.9 on 3D7, 10 microg/ml on Dd2 and had
no effect on lymphocyte proliferation even at the highest tested concentration;
the IC50 was greater than 100 microg/ml. Liquid-liquid separation of the
methanolic extract of M. senegalensis revealed that the dichloromethane extract
possessed an IC50 value of only 2.1 microg/ml. Column fractionation of
dichloromethane extract gave four fractions and fraction two showed an IC50
value of 0.5 microg/ml. Preliminary phytochemical analysis of dichloromethane
fraction revealed terpenoids and traces of phenolic principles but no alkaloid,
tannins or flavonoids were detected.

Publication Types:
In Vitro

PMID: 10363837 [PubMed - indexed for MEDLINE]

227: Phytother Res. 1999 Feb;13(1):81-3.

Prolonged murine genotoxic effects of crude extracted from neem.

Awasthy KS, Chaurasia OP, Sinha SP.

Department of Zoology, KKM College, Pakur, India.

Oral administration of a crude ethanol extract of the leaves of neem
(Azadirachta indica A juss) to adult Swiss albino mice for 7 days at 5 mg, 10 mg
or 20 mg/10 g bw/day significantly increased the incidence of structural and
mitosis disruptive changes in metaphase chromosomes of bone marrow cells on days
8, 15 and 35th of observation. It is proposed that one or other of the many
constituents of the extract, along with genera free radicals, interfered with
DNA to yield chromosome strand breakage or produced spindle disturbances,
inducing belated genotoxic effects.

PMID: 10189960 [PubMed - indexed for MEDLINE]

228: Indian J Exp Biol. 1998 Nov;36(11):1151-3.

Immunopotentiating effects of Azadirachta indica (Neem) dry leaves powder in
broilers, naturally infected with IBD virus.

Sadekar RD, Kolte AY, Barmase BS, Desai VF.

Department of Pharmacology & Medicine, Dr Panjabrao Deshmukh Krishi Vidyapeeth,
Akola, India.

Effects of feeding of powdered dry leaves of A. indica (AI) were investigated on
humoral and cell mediated immune responses, in a flock of broilers which had
survived an outbreak of infectious bursal disease (IBD). AI (2 g/kg) treatment
significantly enhanced the antibody titres against new castle disease virus
(NCDV) antigen and also potentiated the inflammatory reactions to 1.
Chloro-2,4-di- nitro benzene (DNCB) inskin contact test. The results indicate
that AI could be beneficial in immunosuppressed condition like IBD, in poultry.

PMID: 10085786 [PubMed - indexed for MEDLINE]

229: Br Poult Sci. 1998 Dec;39(5):648-52.

Neem (Azadirachta indica) kernel meal in the diet of White Leghorn layers.

Gowda SK, Verma SV, Elangovan AV, Singh SD.

Central Avian Research Institute, Izatnagar, India.

1. Neem kernel meal (NKM) was incorporated into a standard layer diet at 0, 100,
150 and 200 g/kg, replacing parts of the soyabean meal and deoiled rice bran.
Each diet was offered to 18 White Leghorn layers (25 weeks, 50% egg production)
in individual cages for a period of 12 weeks. 2. Results indicated significantly
lower food intakes (P < 0.01), rates of egg production and egg weights in birds
fed on the diets with NKM at 150 and 200 g/kg. Fertility and hatchability were
also adversely affected by the higher inclusion rates of NKM. 3. Except for
lower egg shell weight and shell thickness (P < 0.05) in hens fed NKM at 150 and
200 g/kg, the internal egg quality characteristics were comparable in all
groups. 4. Feeding NKM beyond 100 g/kg to laying hens significantly (P < 0.01)
reduced the content of haemoglobin, erythrocyte count, packed cell volume, serum
calcium and uric acid concentrations. However, the leucocyte count, plasma
glucose concentration and serum glutamate oxaloacetate transaminase activity
were unaltered. Serum glutamate pyruvate transaminase activity was significantly
(P < 0.05) reduced in birds fed NKM at 200 g/kg. 5. Thus NKM at 100 g/kg in a
layer diet would appear to be safe and cost-effective.

PMID: 9925318 [PubMed - indexed for MEDLINE]

230: Acta Trop. 1999 Jan 15;72(1):39-52.

Plant products used as mosquito repellents in Guinea Bissau, West Africa.

Palsson K, Jaenson TG.

Department of Zoology, Uppsala University, Sweden.

By standardized interviews of people in 23 rural villages, in the Oio region of
Guinea Bissau, we collected data on which plant species and plant derived
products or methods people use to reduce mosquito biting activity.The following
plants were used to reduce numbers of mosquitoes indoors at night: fresh or
smouldering Hyptis suaveolens Poit. (Lamiaceae), smoke of the bark of Daniellia
oliveri Rolfe (Caesalpiniaceae), smoke of the infructescence of Elaeis
guineensis Jacq. (Arecaceae), smoke of the seed capsules of Parkia biglobosa
(Jacq.) Benth. (Mimosaceae), smoke of the leaves of Azadirachta indica A.Juss.
(Meliaceae) and Eucalyptus sp. (Myrtaceae), fresh Ocimum canum Sims (Lamiaceae),
and fresh Senna occidentalis (L.) Link (Caesalpiniaceae). In two field
experiments we estimated the 'repellent activity' of certain of these plants and
compared their efficacies with those of two commercially available mosquito
repellents, i.e. 'positive' controls. In the first experiment we tested:
smouldering H. suaveolens (85.4% repellency); fresh H. suaveolens (73.2%);
burning of the bark of D. oliveri (74.7%); and smoke of the leaves of Eucalyptus
(72.2%). In the second experiment we tested: smouldering H. suaveolens (83.6%
repellency); fresh H. suaveolens (66.5%); burning of the bark of D. oliveri
(77.9%); smoke of the leaves of A. indica (76.0%); smoke of the infructescence
of E. guineensis (69.0%); fresh O. canum (63.6%); and fresh S. occidentalis;
(29.4%). All the products tested, except S. occidentalis were significantly more
effective than the negative control.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9924960 [PubMed - indexed for MEDLINE]

231: J Vector Ecol. 1998 Dec;23(2):114-22.

Antifeedancy of neem products containing Azadirachtin against Culex tarsalis and
Culex quinquefasciatus (Diptera: Culicidae).

Su T, Mulla MS.

Department of Entomology, University of California, Riverside 92521-0314, USA.

In order to develop and utilize new botanical insecticides originating from neem
(Azadirachta indica A. Juss) in mosquito control programs as a potential
larvicide, the antifeedant activity of three formulations of neem against the
larvae of Culex tarsalis Coquillett and Culex quinquefasciatus Say was
investigated under laboratory conditions. A significant antifeedancy was
indicated at 5 ppm and 10 ppm azadirachtin (AZ) for all formulations and both
species. Within the test concentration range of AZ (1-10 ppm), 5 ppm was the
minimum effective concentration for antifeedancy in most cases. Some differences
in larval susceptibility in terms of antifeedancy to the test formulations were
noted between the two species. The Cx. tarsalis larvae were more susceptible
than Cx. quinquefasciatus larvae to Azad EC 4.5 at 1 ppm during the first 15-min
exposure period and at 5 and 10 ppm during the whole test period. The Cx.
quinquefasciatus larvae were more susceptible than Cx. tarsalis larvae to Azatin
WP 4.5 at 1, 5, and 10 ppm during the first 15-min exposure period or to Neemix
EC 4.5 at 1 ppm during the first 45-min exposure period. The formulation-related
differences in antifeedant activity appeared when the concentration increased
from 1 to 10 ppm. In Cx. tarsalis, the Azad EC 4.5 and Neemix EC 4.5 were more
effective than Azatin WP 4.5 at 5 ppm during the first 15-min exposure period
and at 10 ppm during the whole test period. In Cx. quinquefasciatus, the Azatin
WP 4.5 and Neemix EC 4.5 were more effective than Azad EC 4.5 at 1 ppm during
the first 30-min exposure period, and at 5 ppm during the first 60-min exposure
period, and at 10 ppm during the whole test period.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9879068 [PubMed - indexed for MEDLINE]

232: Arch Environ Contam Toxicol. 1998 Oct;35(3):426-31.

The toxicity of margosan-O, a product of neem seeds, to selected target and
nontarget aquatic invertebrates

Scott IM, Kaushik NK.

Department of Environmental Biology, University of Guelph, Guelph, Ontario,
Canada, N1G 2W1.

Margosan-O, an insecticide formulated from extracts of neem tree (Azadirachta
indica) seed kernels, besides being toxic, also has feeding,
oviposition-deterring, and growth-inhibitory effects on insects. This product,
registered in the United States for ornamental plants, has been proposed for
food crop use. However, little information exists on its effects on aquatic
organisms. This study investigated toxicity of Margosan-O to the mosquito Culex
spp., a possible target species, and to nontarget species-two crustaceans,
Daphnia magna, Hyalella azteca, and a dipteran, Chironomus riparius. The 48-h
EC50 value of 105 mg L-1 for Culex spp. was significantly more toxic than for C.
riparius (281 mg L-1), not significantly different from D. magna (125 mg L-1)
but was significantly less toxic than for H. azteca (71 mg L-1). A concentration
of 20-30 mg L-1 caused growth inhibitory effects in Culex spp. and C. riparius
larvae and 40 and 84 mg L-1 affected growth and reproduction in H. azteca and D.
magna, respectively. Margosan-O may not be suitable for mosquito control since
the concentrations required to control emergence may have some nontarget
effects. Alternatively, the agricultural application of Margosan-O is also not
expected to reduce the survival or produce growth and reproductive effects in
nontarget aquatic organisms. However, based on estimated concentrations of less
than 10 mg L-1 in adjacent shallow bodies of water and recommendations for
repeated applications, there should be concern that the threshold for chronic
toxicity is too narrow.

PMID: 9732473 [PubMed - as supplied by publisher]

233: Indian J Exp Biol. 1998 Apr;36(4):418-20.

Possible biochemical mode of anti-inflammatory action of Azadirachta indica A.
Juss. in rats.

Chattopadhyay RR.

Biometry Research Unit, Indian Statistical Institute, Calcutta, India.

The water soluble part of alcoholic extract of A. indica leaves at a dose of 200
mg/kg, p.o., exerted significant antiinflammatory activity in cotton pellet
granuloma assay in rats. The extract also inhibited significantly the
biochemical parameters (viz. DNA, RNA, lipid peroxide, acid phosphatase and
alkaline phosphatase) studied in cotton pellet exudate.

PMID: 9717455 [PubMed - indexed for MEDLINE]

234: J Ethnopharmacol. 1998 Jul;61(3):173-8.

In vitro antiplasmodial activity of stem and root extracts of Nauclea latifolia
S.M. (Rubiaceae).

Benoit-Vical F, Valentin A, Cournac V, Pelissier Y, Mallie M, Bastide JM.

Laboratoire d'Immunologie et Parasitologie, Faculte de Pharmacie, Montpellier,

Aqueous extracts from Nauclea latifolia S.M. (Rubiaceae), a plant commonly used
in Ivory Coast by traditional healers for the treatment of malaria, were tested
on two strains of Plasmodium faliparum: FcB1-Colombia (chloroquine-resistant)
and a Nigerian strain (chloroquine-sensitive). The extracts were obtained from
stems and roots of the plant in two forms, infusion and decoction, both methods
used by most traditional healers. The in vitro activity of N. latifolia extracts
on P. falciparum was assessed both visually and by a radioactive method. The
visual analysis allowed determination of the time of extract action on the
erythrocytic cycle, as well as the parasitic stage of most inhibitory effect.
Similar results were obtained applying fresh, frozen or lyophilized extracts.
The IC50 values determined were within the range already reported for other
antimalarial plants such as Azadirachta indica A. Juss (Meliaceae) or Artemisia
annua L. (Asteraceae). Aqueous extracts of N. latifolia inhibited P. falciparum
(FcB1 strain) mainly at the end of the erythrocytic cycle (32nd to 48th hour).

PMID: 9705007 [PubMed - indexed for MEDLINE]

235: J Ethnopharmacol. 1998 May;61(1):31-9.

Inhibition of the growth and development of asexual and sexual stages of
drug-sensitive and resistant strains of the human malaria parasite Plasmodium
falciparum by Neem (Azadirachta indica) fractions.

Dhar R, Zhang K, Talwar GP, Garg S, Kumar N.

Department of Molecular Microbiology and Immunology, School of Hygiene and
Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.

Neem (Azadirachta indica) has been shown to possess anti-malarial activity. In
this study we systematically evaluated extracts of neem seeds and purified
fractions further enriched in polar or non-polar constituents for their effect
on in vitro growth and development of asexual and sexual stages of the human
malaria parasite Plasmodium falciparum. Use of synchronized stages of parasites
suggested trophozoites/schizonts as the susceptible target stages to various
neem extracts. In addition, all the maturation stages of gametocytes were also
killed by various neem fractions tested. The anti-plasmodial effect of neem
components was also observed on parasites previously shown to be resistant to
other anti-malarial drugs, i.e. chloroquine and pyrimethamine suggesting a
different mode of action. Neem seed fractions are thus active not only against
the parasite stages that cause the clinical infection but also against the
stages responsible for continued malaria transmission.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 9687079 [PubMed - indexed for MEDLINE]

236: Food Chem Toxicol. 1998 Jun;36(6):475-84.

Effects of neem flowers, Thai and Chinese bitter gourd fruits and sweet basil
leaves on hepatic monooxygenases and glutathione S-transferase activities, and
in vitro metabolic activation of chemical carcinogens in rats.

Kusamran WR, Ratanavila A, Tepsuwan A.

Biochemistry and Chemical Carcinogenesis Section, Research Division, National
Cancer Institute, Bangkok, Thailand.

The objectives of this study were to determine the effects of feeding of four
vegetables commonly consumed in Thailand, namely, flowers of the neem tree
(Azadirachta indica var. siamensis), fruits of Thai and the Chinese bitter gourd
(Momordica charantia Linn.) and leaves of sweet basil (Ocimum basilicum Linn) on
the levels of phase I enzymes, which include cytochrome P450 (P450), aniline
hydroxylase (ANH) and aminopyrine-N-demethylase (AMD) as well as the capacity to
activate the mutagenicities of aflatoxin B1 (AFB1) and benzo[a]pyrene (BaP), and
to induce the phase II enzymes [i.e. glutathione S-transferase (GST)] in rat
liver. It was found that feeding of the diets containing 12.5% neem flowers and
Thai bitter gourd fruits for 2 weeks strongly enhanced GST activity, 2.7- and
1.6- fold of the pair-fed control values, respectively, while resulting in a
marked reduction of the levels of most phase I reactions. Fruits of the Chinese
bitter gourd, which is in the same species as Thai bitter gourd, had no effect
on GST activity but decreased AMD activity and the in vitro metabolic activation
of AFB1 and BaP. On the other hand, however, dietary sweet basil leaves caused a
significant increase in the levels of both GST and all phase I enzymes. Results
in the present study clearly demonstrate that neem flowers and Thai bitter gourd
fruits contain monofunctional phase II enzyme inducers and compounds capable of
repressing some monooxygenases, especially those involved in the metabolic
activation of chemical carcinogens, while sweet basil leaves contain compounds,
probably bifunctional inducers, capable of inducing both phase I and phase II
enzymes and Chinese bitter gourd fruits contain only compounds capable of
repressing some monooxygenases. These results therefore suggest that neem
flowers and Thai bitter gourd fruits may possess chemopreventive potential,
while those of Chinese bitter gourd fruits and sweet basil leaves are uncertain.

PMID: 9674955 [PubMed - indexed for MEDLINE]

237: J Am Mosq Control Assoc. 1998 Jun;14(2):204-9.

Ovicidal activity of neem products (azadirachtin) against Culex tarsalis and
Culex quinquefasciatus (Diptera: Culicidae).

Su T, Mulla MS.

Department of Entomology, University of California, Riverside 92521-0314, USA.

Bioactive compounds contained in the seed kernel and other parts of the neem
tree (Azadirachta indica A. Juss) have been found to show insecticidal
activities and other effects in many species of insects. These activities
include antifeedancy, growth regulation, fecundity suppression, male sterility,
oviposition repellency, changes in biological fitness such as loss of flying
ability, immunodepression, enzyme inhibition, splitting of biological rhythms,
and so forth. We investigated the ovicidal effects of various formulations of
azadrirachtin (AZ) against the mosquitoes Culex tarsalis Coquillett and Culex
quinquefasciatus Say. The formulations tested were wettable powder Azad WP10,
emulsifiable concentrate Azad EC4.5, and technically pure AZ. The ovicidal
activity of the test neem products was influenced by concentration of AZ, age of
the egg rafts, and age of the neem preparations. Other factors such as
formulation and mosquito species were also involved in the degree of ovicidal
activity. When the egg rafts were deposited directly in fresh neem suspension
and left there for 4 h before transfer to untreated water, 1 ppm of AZ produced
almost 100% mortality in eggs. When egg rafts aged for 0, 4, 8, 12, and 24 h
were exposed to 10 ppm neem suspensions for 36 h, the ovicidal activity was only
attained in the egg rafts deposited directly (0 h old) in the neem suspension,
not in those with ages of 4-24 h. On aging, depending on the formulations and
mosquito species, the neem suspensions at 1 ppm completely lost ovicidal
activity within 7-20 days. The egg rafts of Cx. quinquefasciatus were more
susceptible to the test neem products than those of Cx. tarsalis. The formulated
neem products were more persistent and effective than the technical AZ. The
wettable powder (WP) formulation was slightly more persistent and effective than
the emulsifiable concentrate (EC). The ovicidal activity of the neem products
against mosquitoes from the current research clearly demonstrated the potential
of neem products as possible ovicides against Culex mosquitoes.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9673924 [PubMed - indexed for MEDLINE]

238: Prev Vet Med. 1998 Jun 1;35(3):149-63.

Ethnoveterinary medicines used for ruminants in Trinidad and Tobago.

Lans C, Brown G.

School of Veterinary Medicine, University of the West Indies, St. Augustine,
Trinidad and Tobago.

Ethnoveterinary research was conducted in Trinidad and Tobago in 1995, in order
to document existing ethnoveterinary practices. This paper describes 20
medicinal plants used to treat ruminants. The main plants used were Azadirachta
indica and Curcuma longa. Medicinal plants were used predominantly for
endoparasites, internal and external injuries and pregnancy-related conditions.
A 4-stage process was used to conduct the research and document the
ethnoveterinary practices. This documentation could provide a foundation for the
further scientific study and verification of those practices which merit such

PMID: 9658442 [PubMed - indexed for MEDLINE]

239: J Ethnopharmacol. 1998 Apr;60(3):235-46.

Immunocontraceptive activity guided fractionation and characterization of active
constituents of neem (Azadirachta indica) seed extracts.

Garg S, Talwar GP, Upadhyay SN.

National Institute of Immunology, New Delhi, India.

A novel approach for immunocontraception by intervention of local cell mediated
immunity in the reproductive system by using single intrauterine application of
neem oil has been described earlier. The reversible block in fertility was
reported to last for 107-180 days in female Wistar rats (Upadhyay et al., 1990.
Antifertility effects of neem oil by single intrauterine administration: A novel
method of contraception. Proceedings Of The Royal Society Of London B 242,
175-180) and 7-11 months in monkeys (Upadhyay et al., 1994. Long term
contraceptive effects of intrauterine neem treatment (IUNT) in bonnet monkeys:
An alternative to intrauterine contraceptive devices. Contraception 49,
161-167). The present study, describes the identification and characterization
of the biologically active fraction from neem seeds (Azadirachta indica A. Juss.
Family Meliaceae), responsible for the above activity in adult female Wistar
rats. Initial studies with the mechanically extracted oil and solvent extracts
of neem seeds have revealed that the antifertility activity was present in
constituents of low to intermediate polarity. A hexane extract of neem seeds was
reported to be biologically active (Garg et al., 1994. Comparison of extraction
procedures on the immunocontraceptive activity of neem seed extracts. Journal of
Ethnopharmacology 22, 87-92). Subsequently, hexane extract was sequentially
fractionated through the last active fraction using various separation
techniques and tested for antifertility activity at each step. Preparative HPLC
was used for isolating individual components of the active fraction in
quantities, sufficient for characterization. An analytical HPLC method was
developed for standardization of the fraction. The active fraction was
identified to be a mixture of six components, which comprises of saturated, mono
and di-unsaturated free fatty acids and their methyl esters. Dose response study
was performed with the last active fractions. The antifertility activity with
the active fraction was reversible in nature and it was completely active until
5% concentration. There was no systemic toxic effect following the
administration of the active fraction. This study, for the first time, proposes
an active fraction from neem seeds, responsible for long term and reversible
blocking of fertility after a single intrauterine administration with high

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9613837 [PubMed - indexed for MEDLINE]

240: J Ethnopharmacol. 1998 Feb;60(1):79-84.

Antibacterial activity of East African medicinal plants.

Fabry W, Okemo PO, Ansorg R.

Institut fur Medizinische Mikrobiologie, Universitatsklinikum Essen, Germany.

In an ethnopharmacological survey, extracts of the six East African medicinal
plants Entada abyssinica (stem bark), Terminalia spinosa (young branches),
Harrisonia abyssinica (roots), Ximenia caffra (roots), Azadirachta indica (stem
bark and leaves), and Spilanthes mauritiana (roots and flowers) were tested
against 105 strains of bacteria from seven genera (Staphylococcus, Enterococcus,
Pseudomonas, Escherichia, Klebsiella, Salmonella, Mycobacterium). The minimum
inhibitory concentration reached by 50% (MIC50%) and 90% (MIC90) of the strains
for the extracts of E. abyssinica, T. spinosa, X. caffra, and A. indica (stem
bark) ranged from 0.13-8 mg/ml and from 0.5 to > 8 mg/ml, respectively. Their
minimum bactericidal concentration by 50% (MBC50%) and MBC90% were all between
0.5 and > 8 mg/ml. H. abyssinica, A. indica (leaves), and S. mauritiana (roots
and flowers) had MIC and MBC values > or = 8 mg/ml. Mycobacteria were not
inhibited at extract concentrations of 0.5-2 mg/ml. It is concluded that plant
extracts with low MIC and MBC values may serve as sources for compounds with
therapeutic potency.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9533435 [PubMed - indexed for MEDLINE]

241: Indian J Physiol Pharmacol. 1997 Jul;41(3):234-40.

Effects of Azadirachta indica leaves on the seminal vesicles and ventral
prostate in albino rats.

Kasutri M, Ahmed RN, Pathan KM, Shaikh PD, Manivannan B.

Department of Zoology, Karnatak University, Dharwad.

Oral administration of 20, 40, 60, mg of dry Azadirachta indica leaf powder for
24 days resulted in decrease in the weights of seminal vesicles and ventral
prostate, reduction in epithelial height, nuclear diameter and the secretory
material in the lumen. Biochemically, there was a decrease in total protein,
acid phosphatase activities. Seminal vesicles and ventral prostate being
androgen dependent, the regressive changes histologically as well as
biochemically, suggests the antiandrogenic property of the neem leaves.

PMID: 10232767 [PubMed - indexed for MEDLINE]

242: Am J Reprod Immunol. 1997 Jun;37(6):485-91.

Induced termination of pregnancy by purified extracts of Azadirachta Indica
(Neem): mechanisms involved.

Talwar GP, Shah S, Mukherjee S, Chabra R.

International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali
Marg, New Delhi, India.

PROBLEM: To develop a self-administered, orally delivered method for abrogation
of early pregnancy. METHOD: Use of purified Neem extracts containing
immunomodulators stimulating Th1 cells and macrophages; test animals, rats,
baboons, and monkeys, onset of pregnancy confirmed by surgery and counting of
implants on day 7 in rats and by chorionic gonadotropin (CG) and progesterone
assays in primates; termination defined by complete resorption on day 15 in rats
and by bleeding and decline of CG and progesterone in baboons. RESULTS:
Pregnancy was terminated successfully in both rodents and primates with no
significant side effects. Fertility was regained in both species after one or
two irregular cycles. Progeny born had normal developmental landmarks and
mothered normal litters in the course of time. The active principle in Neem has
been partially fractionated by activity-guided purification. A cascade of events
are involved in abrogation of pregnancy. In primates, a decrease in progesterone
is an early event. A transient increase in CD4 and CD8 cells is noted in spleen
at 96 hr and in mostly CD8 cells in mesenteric lymph nodes. Treatment causes an
elevation of both immunoreactive and bioactive TNF-alpha and gamma-interferon in
serum, mesenteric lymph nodes, and foetoplacental tissue. CONCLUSION:
Immunomodulators of plant origin are potentially usable for termination of
unwanted pregnancy

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9228306 [PubMed - indexed for MEDLINE]

243: J Nat Prod. 1997 Apr;60(4):336-41.

Antimalarial activity of tropical Meliaceae extracts and gedunin derivatives.

MacKinnon S, Durst T, Arnason JT, Angerhofer C, Pezzuto J, Sanchez-Vindas PE,
Poveda LJ, Gbeassor M.

Ottawa-Carleton Institutes of Chemistry and Biology, University of Ottawa,
Ontario, Canada.

Extracts of 22 species of Meliaceae were examined for antimalarial activity
using in vitro tests with two clones of Plasmodium falciparum, one sensitive to
chloroquine (W2) and one chloroquine-resistant (D6). Twelve extracts were found
to have activity, including extracts of Cedrela odorata wood and Azadirachta
indica leaves, which contained the limonoid gedunin. These extracts were more
effective against the W2 clone than the D6 clone, suggesting there is no
cross-resistance to chloroquine. Gedunin was extracted in quantity, and nine
derivatives prepared for a structure-activity study, which revealed essential
functionalities for activity. The study also included four other limonoids
derived from related Meliaceae. Only gedunin had better activity than
chloroquine against the W2 clone. This active principle could be used to
standardize a popular crude drug based on traditional use of A. indica in West

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9134742 [PubMed - indexed for MEDLINE]

244: Immunol Cell Biol. 1997 Apr;75(2):190-2.

Plant immunomodulators for termination of unwanted pregnancy and for
contraception and reproductive health.

Talwar GP, Raghuvanshi P, Misra R, Mukherjee S, Shah S.

Reproductive Health and Vaccinology Division, International Centre for Genetic
Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India.

Neem (Azadirachta indica) seed and leaf extracts have spermicidal,
anti-microbial, anti-fungal and anti-viral properties. They are also
immunomodulators that induce primarily a TH1 type response. These properties are
being exploited to develop two different useful methods of fertility control.
Neem extracts given orally at early post-implantation stage terminate pregnancy
in rodents and primates. Treatment has no residual permanent effect and
fertility is regained in subsequent cycles. The mechanism by which the action
occurs is not fully clear. A transient increase in CD4 and more significantly in
CD8 cells is noticed in mesenteric lymph nodes and spleen. A rise in
immunoreactive and bioactive TNF-alpha and IFN-gamma in draining lymph nodes,
serum and foetal-placental tissue is observed. A polyherbal cream and pessary
have been developed containing three active ingredients of plant origin. These
have synergistic spermicidal properties on human sperm as determined by the
Sander Cramer test. Their use before mating has high contraceptive efficacy in
rabbits and baboons. Another interesting property is their inhibitory action on
a wide spectrum of micro-organisms, including Candida albicans, C. tropicalis,
Neisseria gonorrhoeae, the multidrug-resistant Staphylococcus aureus and urinary
tract Escherichia coli, Herpes simplex-2 and HIV-1. Phase I clinical trials have
been completed in India, Egypt and the Dominican Republic, and indicate the
safety of the formulation, its acceptability and beneficial action invaginosis
due to infections.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9107574 [PubMed - indexed for MEDLINE]

245: Gen Pharmacol. 1997 Mar;28(3):449-51.

Effect of Azadirachta indica hydroalcoholic leaf extract on the cardiovascular

Chattopadhyay RR.

Biometry Research Unit, Indian Statistical Institute, Calcutta, India.

1. The effect of Azadirachta indica hydroalcoholic leaf extract on the
cardiovascular system was studied. 2. The leaf extract was found to reduce a
dose-dependent hypotensive effect without altering the amplitude or rate of
respiration. 3. In isolated frog heart, there was no noticeable change in
amplitude of contraction or rate of the heart at lower doses of leaf extract.
However, at higher doses, there was temporary cardiac arrest in diastole. 4. The
results are discussed.

Publication Types:
Comparative Study

PMID: 9068989 [PubMed - indexed for MEDLINE]

246: Arch Insect Biochem Physiol. 1997;35(1-2):199-209.

Effects of the neem tree compounds azadirachtin, salannin, nimbin, and
6-desacetylnimbin on ecdysone 20-monooxygenase activity.

Mitchell MJ, Smith SL, Johnson S, Morgan ED.

Department of Biology and Health Services, Edinboro University of Pennsylvania
16444, USA. [email protected]

The effects of azadirachtin, salannin, nimbin, and 6-desacetylnimbin on ecdysone
20-monooxygenase (E-20-M) activity were examined in three insect species.
Homogenates of wandering stage third instar larvae of Drosophila melanogaster,
or abdomens from adult female Aedes aegypti, or fat body or midgut from fifth
instar larvae of Manduca sexta were incubated with radiolabeled ecdysone and
increasing concentrations (from 1 x 10(-8) to 1 x 10(-3) M) of the four
compounds isolated from seed kernels of the neem tree, Azadirachta indica. All
four neem tree compounds were found to inhibit, in a dose-dependent fashion, the
E-20-M activity in three insect species. The concentration of these compounds
required to elicit a 50% inhibition of this steroid hydroxylase activity in the
three insect species examined ranged from approximately 2 x 10(-5) to 1 x

PMID: 9131784 [PubMed - indexed for MEDLINE]

247: J Commun Dis. 1996 Dec;28(4):260-9.

Effects of aqueous extract of deoiled neem (Azadirachta Indica A. juss) seed
kernel and karanja (Pongamia Glabra vent) seed kernel against Culex

Sagar SK, Sehgal SS.

Department of Zoology, University of Delhi.

Aqueous extract obtained from deoiled neem and karanja seed kernels (ADNSD and
ADKSK) were assessed for their toxic and growth regulating activities against Cx
quinquefaciatus treated as first instar larvae. ADNSK at various concentrations
was effective on the growth regulating mechanism, inducing prolonged larval
stages. However, 100% larval mortality was observed, especially during the first
and the second instars at all the tested concentrations. ADKSK caused 100%
mortality in the fourth instar larvae and prepupae at the concentration of 100
ppm with no significant effect on the developmental period. The adults emerging
from treated (50 ppm) larvae were smaller in size and malformed. We found ADNSK
to be more effective than ADKSK.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9057450 [PubMed - indexed for MEDLINE]

248: Natl Med J India. 1996 Nov-Dec;9(6):297.

Cytotoxicity of neem leaf extract (Azadirachta indica, Juss): an antitumour

Gogate SS.

Publication Types:

PMID: 9111794 [PubMed - indexed for MEDLINE]

249: Indian J Exp Biol. 1996 Nov;34(11):1091-4.

Effect of Azadirachta indica leaves on testis and its recovery in albino rats.

Joshi AR, Ahamed RN, Pathan KM, Manivannan B.

Department of Zoology, Karnatak University, Dharwad, India.

Histological and biochemical changes in the testis of rats treated with the leaf
powder of A. indica are reported. The pattern of recovery is also studied at 8,
16 and 24 day after withdrawal of the treatment. In the treated rats, a general
reduction in the diameters of seminiferous tubule, nuclei of the germinal
elements and a mass atrophy of the spermatogenic elements has been observed. The
Leydig cells are found to be atrophic. Biochemically, a decrease in the protein
content and the activity of acid phosphatase and an increase in the total free
sugar, glycogen, cholesterol contents and the activities of alkaline phosphatase
and lactate dehydrogenase have been observed. A gradual recovery is observed in
both the histological and biochemical parameters after 8.16 and 24 day of
cessation of the treatment. The result suggest a possible reversible
antiandrogenic property of the leaves of A. indica in male albino rats.

PMID: 9055629 [PubMed - indexed for MEDLINE]

250: Br Poult Sci. 1996 Sep;37(4):809-18.

Performance of broiler chicks fed on alkali-treated neem (Azadirachta indica)
kernel cake as a protein supplement.

Nagalakshmi D, Sastry VR, Agrawal DK, Katiyar RC, Verma SV.

Division of Animal Nutrition, Indian Veterinary Research Institute, Izatnagar,

1. An experiment was conducted to evaluate growth and nutrient efficiency of
broiler chicks from 3 to 42 d fed on diets containing alkali-treated neem
(Azadirachta indica A. juss) kernel cake (NKC) as a protein supplement in place
of peanut meal (PNM). 2. NKC was treated with sodium hydroxide at 10 (ANKC 1) or
20 g (ANKC 2)/kg and incorporated into the test diets at 135 or 300 g/kg to
replace 50 (low-L) or 100 (High-H)% of the PNM protein of the reference diet. 3.
Despite comparable retentions of dry matter and total carbohydrate on L-ANKC 1
and 2, fibre on L-and H-ANKC 2 and nitrogen, calcium and acid detergent fibre on
all experimental diets compared to the retentions of chicks on the reference
diet, only the chicks fed L-ANKC 2 were found to grow and utilise food as well
as those on the reference diet. 4. The activities of serum alkaline phosphatase
on H-ANKC 1 and alanine amino transferase on all test diets were depressed (P <
0.05), but the activity of serum aspartate amino transferase, total erythrocyte
count and concentration of blood haemoglobin and urea were similar in all
chicks. 5. No significant differences were noticed in the qualitative and
quantitative characteristics of the meat of chicks fed on the reference diet and
on diets incorporating ANKC at the lower concentrations. Feeding ANKC protein
did not impart any untoward taste as evaluated in pressure cooked meat by a
semitrained panel on a 7 point Hedonic scale. 6. Except for duodenal and jejunal
inflammation in chicks on both reference and test diets, all the vital organs
were normal, ruling out any adverse affects caused by residual neem bitters. 7.
Comparable performance and cost of chicks fed on the reference and L-ANKC 2
diets, warrants the utilisation of hitherto wasted protein-rich NKC after alkali
treatment in broiler chick diets to spare peanut meal for human consumption in
developing countries.

PMID: 8894225 [PubMed - indexed for MEDLINE]

251: Chemotherapy. 1996 Sep-Oct;42(5):315-7.

Activity of east African medicinal plants against Helicobacter pylori.

Fabry W, Okemo P, Ansorg R.

Institute of Medical Microbiology, University of Essen, Germany.

The activity of extracts from the East African medicinal plants Entada
abyssinica (stem bark), Terminalia spinosa (young branches), Harrisonia
abyssinica (roots), Ximenia caffra (roots), Azadirachta indica (leaves and stem
bark) and Spilanthes mauritiana (roots and flowers) were evaluated against 12
strains of Helicobacter pylori. The most active extracts were those derived from
T. spinosa with an MIC50 of 125 micrograms/ml, an MIC90 of 250 micrograms/ml and
an MIC range of 62.5-500 micrograms/ml. An MIC50 of 250 micrograms/ml and an
MIC90 of > 4,000 micrograms/ml was reached by H. abyssinica with a range of
125-->4,000 micrograms/ml and by X. caffra with a range of 62.5-->4,000
micrograms/ml, respectively. It is concluded that these plants contain compounds
with antimicrobial activity against H. pylori.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 8874968 [PubMed - indexed for MEDLINE]

252: Biol Trace Elem Res. 1996 Aug;54(2):113-21.

Minor and trace elemental determination in the Indian herbal and other medicinal

Samudralwar DL, Garg AN.

Department of Chemistry, Nagpur University, India.

Medicinal plants described in the Indian "Ayurvedic" literature viz. Tulsi
(Ocimum sanctum), Gulvel (Tinospora cardifolia), bitter Neem (Azadirachta
indica), Kanher (Nerium Andicum), Vekhand (Acorus calamus), and Peacock's
feather (ash) were analyzed for minor and trace elements by instrumental neutron
activation analysis. The samples and the standards from the National Institute
of Standards and Technology, USA and IAEA, Vienna were irradiated for 5 min, 1
h, 5 h, and 10 h with thermal neutrons at a flux of 10(12)-10(13) n cm-2 s-1 in
APSARA and CIRUS reactor at BARC, Bombay. High resolution gamma ray spectrometry
was performed using a 45 cm3 HPGe detector and a 4096 MCA system. Concentrations
of 13 elements were determined. Zinc, manganese, and sodium were significantly
higher in Tulsi leaves while zinc is higher in Neem leaves. Peacock's feathers
were found to be rich in manganese, iron, copper, and zinc. A high concentration
of mercury was also found in the peacock's feather ash. The therapeutic
significance in restoring ionic balance is discussed.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 8886311 [PubMed - indexed for MEDLINE]

253: Indian J Exp Biol. 1996 Jul;34(7):698-701.

Modulation of humoral and cell-mediated immune responses by Azadirachta indica
(Neem) in mice.

Ray A, Banerjee BD, Sen P.

Department of Pharmacology, University College of Medical Sciences (University
of Delhi), Shahdara, Delhi, India.

The effects of A. indica (AI, Neem) were evaluated on tests of humoral and
cell-mediated immune responses after 3 weeks of oral AI (leaf extract) treatment
in ovalbumin immunized mice. At the dose levels tested, AI (10, 30 or 100
mg/kg), had no appreciable influence on different organ (liver, spleen,
thymus)/body weight indices, when compared to controls. In tests for humoral
immune responses, AI (100 mg/kg) treated mice had higher (1) IgM and IgG levels,
and (b) anti-ovalbumin antibody titres, when compared to the vehicle treated
group. In tests for cell-mediated immune responses, there was an enhancement (%)
of (a) macrophage migration inhibition, and (b) footpad thickness after AI (100
mg/kg) treatment. These results are discussed in light of the possible
immunopotentiating effects of AI.

PMID: 8979510 [PubMed - indexed for MEDLINE]

254: Contraception. 1996 Jun;53(6):375-8.

Purified neem (Azadirachta indica) seed extracts (Praneem) abrogate pregnancy in

Mukherjee S, Lohiya NK, Pal R, Sharma MG, Talwar GP.

International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali
Marg, New Delhi, India.

The use of neem (Azadirachta indica) seed extracts (Praneem) given orally for
abrogation of pregnancy in subhuman primates is described. Oral administration
of Praneem was initiated after confirmation of pregnancy using Leydig cell
bioassay estimating rising levels of chorionic gonadotropin (CG) in the blood
from day 25 onwards of the cycle and continued for six days. Termination of
pregnancy was observed with the appearance of blood in the vaginal smears and
decline in CG and progesterone. Pregnancy continued in the control animals
treated with peanut oil at the same dose. The effect was observed in both
baboons and bonnet monkeys. The treatment was well tolerated; blood chemistry
and liver function tests had normal values. The animals regained their normal
cyclicity in the cycles subsequent to Praneem treatment.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 8773426 [PubMed - indexed for MEDLINE]

255: J Ethnopharmacol. 1996 May;52(1):35-40.

Molluscicidal activity of neem (Azadirachta indica A. Juss).

Singh K, Singh A, Singh DK.

Department of Zoology, University of Gorakhpur, U.P., India.

Molluscicidal property of Azadirachta indica A. Juss (neem) against the snails
Lymnaea acuminata and Indoplanorbis exustus was studied. It was observed that
the molluscicidal activity of the leaf, bark, cake, neem oil and the neem-based
pesticides, achook and nimbecidine, was both time- and dose-dependent. The toxic
effect of pure azadirachtin against both the snails was greater than the
synthetic molluscicides.

PMID: 8733117 [PubMed - indexed for MEDLINE]

256: Gen Pharmacol. 1996 Apr;27(3):431-4.

Possible mechanism of antihyperglycemic effect of Azadirachta indica leaf
extract. Part IV.

Chattopadhyay RR.

Biometry Research Unit, Indian Statistical Institute, Calcutta, India.

1. Effect of epinephrine on the increment index calculated from intravenous
glucose tolerance tests and on hepatic glycogen before and after A. indica leaf
extract treatment was studied in normal and streptozotocin-induced diabetic
rabbits. 2. A. indica leaf extract, in itself, was found to have no action on
peripheral utilization of glucose or on hepatic glycogen. 3. The reduction in
peripheral utilization of glucose and glycogenolytic effect due to epinephrine
action was blocked by A. indica leaf extract, however, almost completely in
diabetic rabbits and to a certain extent in normal ones. 4. The results are

PMID: 8723520 [PubMed - indexed for MEDLINE]

257: J Med Entomol. 1996 Mar;33(2):195-201.

Effect of volatiles from neem and other natural products on gonotrophic cycle
and oviposition of Anopheles stephensi and An. culicifacies (Diptera:

Dhar R, Dawar H, Garg S, Basir SF, Talwar GP.

Malaria-Mosquito Biology Laboratory, National Institute of Immunology, New
Delhi, India.

The gonotrophic cycle of female Anopheles was impaired by exposure to volatiles
of neem, (Azadirachta indica), reetha, (Sapindus mukorossi), and garlic, (Allium
sativum), but not to castor seeds and cotton seed oil. A brief exposure to
contact or volatile extracts from neem suppressed rather than inhibited
oviposition. Complete inhibition of oviposition was observed by exposure of
mosquitoes to neem oil and 1 fraction containing volatile components.
Vitellogenesis was impaired irreversably by long-term exposure to neem odor and
some extracts. The effect of volatiles on oviposition seems to be regulated by
absorption through the cuticle, although passage through the spiracles could not
be excluded.

Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 8742520 [PubMed - indexed for MEDLINE]

258: Hindustan Antibiot Bull. 1996 Feb-Nov;38(1-4):53-6.

In vitro evaluation of medicinal plant extracts against Pestalotiopsis

Rai MK.

Department of Botany, Danielson College, Chhindwara, India.

A serious leaf-spot disease of Mangifera indica was noted during the last 10
years in Satpura plateau of India. On the basis of characteristic symptoms and
cultural characters, the pathogen was identified as Pestalotiopsis mangiferae
which is hitherto not reported from Satpura plateau of India. Screening of
17-medicinal plants against the test pathogen revealed 14 antimycotic whereas
3-plants, viz., Argemone mexicana, Caesalpinia bonducella, and Casia fistula
acclerated the growth of the pathogen. The maximum activity was shown by
Eucalyptus globulus (88%) and Catharanthus roseus (88%) followed by Ocimum
sanctum (85.50%), Azadirachta indica (84.66%), Ricinus communis (75%) and
Lawsonia inermis (74.33%) while the minimum activity was exhibited by Jatropha
curcas (10%).

PMID: 9676046 [PubMed - indexed for MEDLINE]

259: J Dent Res. 1996 Feb;75(2):816-22.

The inhibiting effect of aqueous Azadirachta indica (Neem) extract upon
bacterial properties influencing in vitro plaque formation.

Wolinsky LE, Mania S, Nachnani S, Ling S.

Section of Oral Biology, University of California, School of Dentistry, Los
Angeles 90095-1668, USA.

The purpose of this investigation was to examine the inhibitory effects of
aqueous extracts derived from the bark-containing sticks (Neem stick) of
Azadirachta indica upon bacterial aggregation, growth, adhesion to
hydroxyapatite, and production of insoluble glucan, which may affect in vitro
plaque formation. Neem stick extracts were screened for minimal bacterial growth
inhibition (MIC) against a panel of streptococci by means of a broth dilution
assay. Initial bacterial attachment was quantified by the measurement of the
adhesion of 3H-labeled Streptococcus sanguis to saliva-conditioned synthetic
hydroxyapatite. The effect of the Neem stick extract upon insoluble glucan
synthesis was measured by the uptake of radiolabeled glucose from 14C-sucrose.
Aggregating activity of the Neem stick extracts upon a panel of streptococci was
also examined. No inhibition of bacterial growth was observed among the
streptococcal strains tested in the presence of < or = 320 micrograms/mL of the
Neem stick extract. The pre-treatment of S. sanguis with the Neem stick extract
or the gallotannin-enriched extract from Melaphis chinensis at 250 micrograms/mL
resulted in a significant inhibition of the bacterial adhesion to
saliva-conditioned hydroxyapatite. Pre-treatment of saliva-conditioned
hydroxyapatite with the Neem stick or gallotannin-rich extract prior to exposure
to bacteria yielded significant reductions in bacterial adhesion. The Neem stick
extract and the gallotannin-enriched extract from Melaphis chinensis inhibited
insoluble glucan synthesis. Incubation of oral streptococci with the Neem stick
extract resulted in a microscopically observable bacteria aggregation. These
data suggest that Neem stick extract can reduce the ability of some streptococci
to colonize tooth surfaces.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 8655780 [PubMed - indexed for MEDLINE]

260: Cytobios. 1996;86(346):155-65.

Effect of plant extracts and systemic fungicide on the pineapple fruit-rotting
fungus, Ceratocystis paradoxa.

Damayanti M, Susheela K, Sharma GJ.

Department of Life Sciences, Manipur University, Imphal, India.

Antifungal activities of extracts of sixteen plants were tested against
Ceratocystis paradoxa which causes soft rot of pineapples. Xanthium strumarium
was the most effective followed by Allium sativum. The effectiveness of various
extracts against C. paradoxa was in the decreasing order of Meriandra
bengalensis, Mentha piperita, Curcuma longa, Phlogacanthus thyrsiflorus, Toona
ciliata, Vitex negundo, Azadirachta indica, Eupatorium birmanicum, Ocimum
sanctum and Leucas aspera. Extracts of Cassia tora, Gynura cusimba, Calotropis
gigantea and Ocimum canum showed poor fungitoxicity. Ethanol was suitable for
extraction of the inhibitory substance from X. strumarium. Acetonitrile was
highly toxic to this fungus. Millipore filter-sterilized extracts had a more
inhibitory effect on the fungus than the autoclaved samples. Treatment of
pineapple fruits infested with C. paradoxa by X. strumarium extract reduced the
severity of the disease.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9022263 [PubMed - indexed for MEDLINE]

261: Am J Reprod Immunol. 1996 Jan;35(1):51-6.

Termination of pregnancy in rodents by oral administration of praneem, a
purified neem seed extract.

Mukherjee S, Talwar GP.

International Centre for Genetic Engineering and Biotechnology, New Delhi,

PROBLEM: Development of an orally administered abortifacient. METHODS: Subjects
were female Wistar rats, weighing 150 to 200 g at the time of experiments.
Praneem (a purified extract of neem Azadirachta indica) at a dose of 0.6 ml was
given orally from day 8 to 10 after confirming presence and number of implants
surgically on day 7 of pregnancy. The animals were examined again under
anesthesia on day 15 of pregnancy to check the number of developing embryos.
Controls received an equivalent regime of peanut oil. The number and size of
implants were counted five days after treatment. RESULTS: Complete resorption of
embryos was observed on day 15 of pregnancy in every animal treated with Praneem
in contrast to normally developing embryos in rats given peanut oil. In repeat
batch experiments, it was established that the effect of the treatment was
reversible and animals regained fertility in cycles subsequent to treatment with
Praneem. Cytokines of Th1 type, i.e., gamma interferon and TNF, were raised on
administration of Praneem, which may be the probable cause of pregnancy
termination. CONCLUSIONS: Praneem on oral administration can cause termination
of pregnancy in rodents, and the action is probably mediated by TH1 cytokines.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 8789560 [PubMed - indexed for MEDLINE]

262: Mycoses. 1996 Jan-Feb;39(1-2):67-70.

Fungistatic and fungicidal activity of east African medicinal plants.

Fabry W, Okemo P, Ansorg R.

Institute of Medical Microbiology, University of Essen, Germany.

Extracts of the traditionally used medicinal plants Entada abyssinica (stem
bark), Terminalia spinosa (young branches), Harrisonia abyssinica (roots),
Ximenia caffra (roots), Azadirachta indica (stem bark), Zanha africana (stem
bark) and Spilanthes mauritiana (roots and flowers) were investigated for
fungistatic and fungicidal activity against Candida spp. and Aspergillus spp. by
a microtitre serial dilution technique. Entada abyssinica, T. spinosa, X.
caffra, A. indica, and Z. africana showed activity against various Candida
species. The minimum inhibitory concentrations (MICs) ranged from 0.006 to > 8
mg ml-1 and the minimum fungicidal concentrations (MFCs) from 0.06 to > 8 mg
ml-1. Extracts from S. mauritiana (both roots and flowers) exhibited no activity
against Candida spp., but against Aspergillus spp., the MIC and MFC values
ranged from 0.13 to 0.25 mg ml-1 and from 0.13 to 1 mg ml-1 respectively. It is
concluded that the extracts contain compounds with high antifungal potency.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 8786762 [PubMed - indexed for MEDLINE]

263: Am J Trop Med Hyg. 1996 Jan;54(1):67-71.

In vitro antimalarial activity of vegetal extracts used in West African
traditional medicine.

Benoit F, Valentin A, Pelissier Y, Diafouka F, Marion C, Kone-Bamba D, Kone M,
Mallie M, Yapo A, Bastide JM.

Laboratoire d'Immunologie et Parasitologie, Unite de Formation et de Recherche
des Sciences Pharmaceutiques, Montpellier, France.

Among strategies for the development of new antimalarials, a study of plants
traditionally used in Africa against malaria has been pursued. Extracts obtained
from the plants Azadirachta indica, Cinnamonum camphora, Lippia multiflora,
Vernonia colorata, Guiera senegalensis, Combretum micranthum, and Ximenia
americana, commonly used in Cote d'Ivoire by native healers for the treatment of
malaria, were tested on two strains of Plasmodium falciparum: FcB1-Colombia
(chloroquine-resistant) and F32-Tanzania (chloroquine-sensitive). Extracts were
obtained after infusion and decoction, both techniques being used by most native
healers. The antimalarial activities of the extracts were tested first by
parasite 3H-hypoxanthine incorporation and second by visual evaluation of the
activities of plant extracts on thin blood smears, which also permitted the
determination of parasitic stages and parasite alteration. Among the seven
plants tested, some had an apparent inhibitory effect on P. falciparum growth in
vitro, while other seemed to be less efficient.

PMID: 8651373 [PubMed - indexed for MEDLINE]

264: Indian J Exp Biol. 1995 Nov;33(11):848-50.

Antinociceptive action of Azadirachta indica (neem) in mice: possible mechanisms

Khanna N, Goswami M, Sen P, Ray A.

Department of Pharmacology, U.C.M.S. & G.T.B. Hospital, Shahdara, Delhi, India.

Azadirachta indica (AI, Neem) was tested for analgesic potency in experimental
pain models in mice. In the glacial acetic acid (GAA) induced writhing test, AI
(10, 30 and 100 mg/kg) dose-dependently reduced both the incidence and the
number of writhes. Similarly, AI, at the dose levels tested, also enhanced tail
withdrawal latencies in the tail-flick test for nociception. In the interaction
studies, pretreatment with the opioid antagonist, naloxone (1 mg/kg) and the
central noradrenaline depleter, DSP-4 (50 mg/kg) attenuated AI analgesia by
differential degrees in both experimental models, whereas, the serotonin
synthesis inhibitor, PCPA (300 mg/kg) potentiated the same. These results
suggest that both central and peripheral mechanisms and complex neural pathways,
opioid and non-opioid, may be involved in AI induced analgesia.

PMID: 8786160 [PubMed - indexed for MEDLINE]

265: Indian J Exp Biol. 1995 Oct;33(10):725-9.

Changes in epididymal structure and function of albino rat treated with
Azadirachta indica leaves.

Kasturi M, Manivannan B, Ahamed RN, Shaikh PD, Pathan KM.

Department of Zoology, Karnatak Science College, Dharwad, India.

The histological and biochemical changes in the caput and cauda epididymis of
albino rat treated with 20, 40 and 60 mg dry powder of the leaves of A. indica
per day for 24 days are reported. In the treated rats, the height of the
epithelium and the diameter of the nucleus in both the regions were reduced. The
lumen of the caput was packed with lymphocytes. Biochemically, a decrease in the
protein content and acid phosphatase activity and an increase in the alkaline
phosphatase and lactate dehydrogenase activities were observed in both the
regions. The effect was dose dependent. Further, serum testosterone
concentration in the higher dose treated animals decreased significantly. The
results suggest a possible antiandrogenic property of the leaves of A. indica.

PMID: 8575802 [PubMed - indexed for MEDLINE]

266: Indian J Malariol. 1995 Sep;32(3):99-103.

Use of neem oil as a mosquito repellent in tribal villages of mandla district,
madhya pradesh.

Mishra AK, Singh N, Sharma VP.

Malaria Research Centre (Field Station), Medical College Building, Jabalpur,

A field study was carried out to evaluate the mosquito repellent action of neem
(Azadirachta indica) oil in tribal forested villages of District Mandla. Various
concentrations of neem oil mixed in coconut oil (1-4%) were applied to the
exposed body parts of human volunteers. Results revealed 81-91% protection
during 12 h period of observation from the bites of anopheline mosquitoes. Neem
oil is an indigenous product and a practical solution to curtail mosquito

PMID: 8936291 [PubMed - indexed for MEDLINE]

267: Plant Foods Hum Nutr. 1995 Jul;48(1):1-16.

Influence of insecticidal plant materials used during storage on sensory
attributes and instrumental hardness of dry edible beans (Phaseolus vulgaris

Dunkel FV, Serugendo A, Breene WM, Sriharan S.

Department of Entomology, Montana State University, Bozeman 59717, USA.

Three plant products with known insecticidal properties, a dry extract of
flowers of Chrysanthemum cinerariaefolium (Trevir.) Vis. produced in Rwanda, an
ethanol extract of seeds of neem, Azadirachta indica A. Juss, and crushed leaves
of Tetradenia riparia Hochst Codd, a traditional Rwandan medicine, were mixed
with beans, Phaseolus vulgaris L., for storage protection. These plant-protected
beans were compared with "off the shelf' beans that were being sold to consumers
by the Rwandan National Agricultural Products Marketing Organization (OPROVIA).
A trained sensory panel determined that beans treated with neem and C.
cinerariaefolium were as acceptable after 8 months storage as those being sold
throughout Rwanda by the marketing organization. Beans marketed by this
organization were all treated with the standard insecticide application in
Rwanda, 0.01% weight/weight pirimiphos methyl in a powder formulation.
Instrumental hardness (% hard-to-cook/mean gram force) after 20 months of
storage was acceptable for beans stored with neem or with C. cinerariaefolium or
with the conventional government application of pirimiphos methyl. Use of either
neem or C. cinerariaefolium for storage protection should not affect consumer
acceptance of dry beans.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 8719734 [PubMed - indexed for MEDLINE]

268: Indian J Malariol. 1995 Jun;32(2):64-9.

Control of mosquito breeding using wood scrapings treated with neem oil.

Nagpal BN, Srivastava A, Sharma VP.

Malaria Research Centre, Delhi, India.

Wood scrapings were given shape of a ball and soaked in 5, 10 and 20% neem
(Azadirachta indica) oil diluted in acetone. Control of Anopheles stephensi and
Aedes aegypti breeding in water storage overhead tanks (OHTs) with the
application of these balls was achieved for 45 days. Two balls soaked in 5% neem
oil produced the best results among other concentrations tested.

PMID: 7589730 [PubMed - indexed for MEDLINE]

269: Afr J Health Sci. 1995 May;2(2):309-311.

In vitro antimalarial activity of extracts of Albizia gummifera, Aspilia
mossambicensis, Melia azedarach and Azadirachta indica against Plasmodium

Ofulla AV, Chege GM, Rukunga GM, Kiarie FK, Githure JI, Kofi-Tsekpo MW.

Biomedical Sciences Research Centre, Kenya Medical Research Institute, P. O. Box
54840, Nairobi, Kenya.

Since chemotherapy is presently the primary strategy of malaria control in the
world, and some malaria parasites are developing resistance to the commonly used
antimalarial drugs, new antimalarial compounds are required. Therefore, it is
important to test antimalarial activities of medicinal plant extracts which most
herbalists claim to cure malaria. We evaluated the antimalarial activities of
extracts of Albizia gummiffera, Aspilia mossambicensis, Melia azedar and
Azadirahchta indica against laboratory adapted isolates of Plasmodium falciparum
using an in vitro radioisotopic uptake technique. Chloroquine was used as a
reference antimalarial drug. Al. gummifera had the highest antimalarial activity
(mean fifty percent inhibitory concentration {IC(50)S} in ug/ml of test culture
=3.5 +1.6SD, n=3) followed by As. mossambicensis (mean IC(50)=29.3+11.8SD, n=4)
and Me. Azedarach (mean IC(50) =299.7+202.0SD, n=4). And lastly Az. Indica (mean
IC(50)=349.9+213.1 SD, n=4). The antimalarial activities of the reference drug,
chloroquine, was far much higher (mean IC(50)=0.065+0.057SD, n=)4). These
findings show that Al. gummifera and As. mossambicensis plant extracts have
potent antimalarial compounds. Phytochemical analyses should be done on these
two plants to isolate the compound(s) containing he active principles(s).

PMID: 12160442 [PubMed - as supplied by publisher]

270: Mycoses. 1995 May-Jun;38(5-6):191-5.

Preliminary studies of the antifungal activities of some medicinal plants
against Basidiobolus and some other pathogenic fungi.

Nwosu MO, Okafor JI.

Department of Botany, University of Nigeria, Nsukka, Nigeria.

The antifungal activities of extracts of 10 medicinal plants collected from
south-eastern parts of Nigeria were tested against seven pathogenic fungi using
the broth dilution and agar plate methods. All the extracts at 1:10 dilution
inhibited the growth of Basidiobolus haptosporus and B. ranarum but did not
inhibit that of Aspergillus fumigatus, Geotrichum candidum and Candida albicans.
While extracts from Piper guineense, Ocimum gratissimum, Moringa oleifera and
Erythrophleum suaveolens inhibited the growth of Trichophyton rubrum and T.
mentagrophytes, those from Fatropha curcas, Mitracarpus villosus, Azadirachta
indica and Gongronema latifolium failed to do so at 1:10 dilution. Extract from
Piper sp. was also able to inhibit the growth of B. haptosporus at a
concentration as low as 1:80 dilution followed by those of Ocimum and Rauvolfia
spp. at 1:40 dilution. These results indicate possible use of certain plant
extracts in the treatment of subcutaneous phycomycosis in humans and animals.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 8531930 [PubMed - indexed for MEDLINE]

271: Trans R Soc Trop Med Hyg. 1995 Mar-Apr;89(2):217-8.

Antimalarial activity in vitro of Cochlospermum tinctorium tubercle extracts.

Benoit F, Valentin A, Pelissier Y, Marion C, Dakuyo Z, Mallie M, Bastide JM.

Laboratoire d'Immunologie et Parasitologie, Faculte de Pharmacie, UFR Sciences
Pharmaceutiques, Montpellier, France.

Resistance of Plasmodium falciparum to current antimalarial compounds has
drastically increased during the last few years and is now a major public health
problem. We have studied plants traditionally used in Africa against malaria.
Extracts of the tubercles of Cochlospermum tinctorium A. Rich, commonly used in
Burkina Faso, were tested in vitro on 2 strains of P. falciparum, one
(FcB1-Colombia) chloroquine resistant and the other (F32-Tanzania) chloroquine
sensitive. Extracts were obtained by infusion and decoction. The 50% inhibitory
concentrations (IC50) were determined by measuring [3H]hypoxanthine
incorporation and also by microscopical examination which permitted the
determination of parasite stages. We obtained similar results with fresh
extracts, frozen extracts, and lyophilized extracts of C. tinctorum. IC50 values
were of the order of 1-2 micrograms/mL, about one-tenth of those reported for
extracts of neem leaves (Azadirachta indica) and about half the values reported
for Artemisia annua extracts.

PMID: 7778154 [PubMed - indexed for MEDLINE]

272: Med Vet Entomol. 1995 Jan;9(1):25-33.

Development of combined use of neem (Azadirachta indica) and water management
for the control of culicine mosquitoes in rice fields.

Rao DR, Reuben R, Nagasampagi BA.

Centre for Research in Medical Entomology, Chinna Chokkikulam, Madurai, India.

Crude neem products have earlier shown considerable promise for control of
culicine mosquito vectors in rice fields as a by-product of their agricultural
use as fertilizers, but suffer from disadvantages of bulkiness and lack of
stability in storage. Relatively stable lipid-rich fractions of neem were shown
to be as effective as good-quality crude neem products in control of breeding of
culicine vectors of Japanese encephalitis, and also produced a slight but
significant reduction in populations of anopheline pupae. Neem-based
formulations coated over urea significantly increased grain yield, but used
alone did not, whereas combining the use of neem-coated urea and water
management by intermittent irrigation had a greater effect on grain yield than
that of water management alone. The neem fractions were relatively
cost-effective, and the combined water management and neem-coated urea strategy
is acceptable to farmers, who are already aware of the benefits of the use of
neem-coated urea, and of water management. This technology therefore has
considerable promise as an environmentally benign method of rice-field mosquito
control that could be sustainably implemented by farmers.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 7696685 [PubMed - indexed for MEDLINE]

273: Southeast Asian J Trop Med Public Health. 1994 Dec;25(4):755-9.

Larvicidal potential of five Philippine plants against Aedes aegypti (Linnaeus)
and Culex quinquefasciatus (Say).

Monzon RB, Alvior JP, Luczon LL, Morales AS, Mutuc FE.

Department of Parasitology, College of Public Health, University of the
Philippines, Manila.

Five species of Philippine plants, reported in the literature to have
insecticidal properties, were selected for investigation, namely: Anona squamosa
("atis" or sugar apple), Eucalyptus globulus ("bagras" or olive gum eucalyptus),
Lansium domesticum ("lansones"), Azadirachta indica ("neem") and Codiaeum
variegatum ("San Francisco" or croton). These were screened and assayed for
their larvicidal potential against Aedes aedes aegypti (Linnaeus) and Culex
quinquefasciatus (Say) by exposing 3rd-4th instar larvae to seven different
concentrations (two-fold dilutions starting from 100 g% up to 1.5625 g%) of the
crude aqueous extract derived from fresh leaves. Three trials were performed for
each species of mosquito and for each of the five plants to determine the
average mortality rate at various concentrations after 24 and 48 hours exposure.
Probit analysis using the NCSS program was employed to determine the LD50 and
LD90 values in order to compare the larvicidal potency of the five plants and to
compare the susceptibility of Ae. aegypti and Cx. quinquefasciatus. The extracts
exerted maximum insecticidal activity after 48 hours exposure. Lansones and atis
were the most effective against larvae of Ae. aegypti and Cx. quinquefasciatus,
respectively. Ae. aegypti was more susceptible than Cx. quinquefasciatus with
respect to lansones and neem but Cx. quinquefasciatus was more susceptible than
Ae. aegyti with respect to eucalyptus, San Francisco and atis. These varying
results are probably due to differences in levels of toxicity among the active
insecticidal ingredients of each plant and in the physiological characteristics
of the two mosquito species.

Publication Types:
Comparative Study

PMID: 7667727 [PubMed - indexed for MEDLINE]

274: J Ethnopharmacol. 1994 Oct;44(2):87-92.

Comparison of extraction procedures on the immunocontraceptive activity of neem
seed extracts.

Garg S, Talwar GP, Upadhyay SN.

National Institute of Immunology, New Delhi, India.

Azadirachta indica (Neem) seed extracts are known to activate the local
cell-mediated immune reactions after a single intrauterine administration,
leading to a long term reversible block of fertility. In order to identify and
characterize the active fraction responsible for this activity, neem seeds were
extracted by both mechanical expression and solvent extraction using a range of
polar to non-polar solvents which yielded 3 broad fractions. The mechanically
expressed oil was fractionated using different approaches and studied for
antifertility activity. The hexane extract and a corresponding column fraction
showed potent and reproducible antifertility activity. Other fractions were less
stable with regard to reproducibility of effects and composition. It is our
conclusion that for subsequent fractionation to reach the last active fraction,
the hexane extract is the most useful starting material.

PMID: 7853869 [PubMed - indexed for MEDLINE]

275: West Indian Med J. 1994 Sep;43(3):71-4.

Effect of aqueous neem (Azadirachta indica) extract on testosterone and other
blood constituents in male rats. A pilot study.

Parshad O, Singh P, Gardner M, Fletcher C, Rickards E, Choo-Kang E.

Department of Physiology, U.W.I., Jamaica.

Effect of oral administration of crude aqueous neem extract on serum
testosterone and other blood constituents was studied in the male Wistar rats
for 10 weeks. The neem treatment resulted in significant decreases (p < 0.01) in
total testosterone, total bilirubin and K+ in serum. There were also increases
(p < 0.05) in packed cell volume, mean corpuscular haemoglobin concentration,
red blood cell, white blood cell and lymphocyte counts without showing any
cytotoxic effects in the body.

PMID: 7817539 [PubMed - indexed for MEDLINE]

276: FEMS Microbiol Lett. 1994 Jul 15;120(3):267-73.

Sexual development of malaria parasites is inhibited in vitro by the neem
extract azadirachtin, and its semi-synthetic analogues.

Jones IW, Denholm AA, Ley SV, Lovell H, Wood A, Sinden RE.

Department of Biology, Imperial College of Science, Technology and Medicine,
London, UK.

We have shown that azadirachtin, a compound from the neem tree, Azadirachta
indica, and selected semi-synthetic derivatives, block the development of the
motile male malarial gamete in vitro. Changes in the hemiacetal group at
position C11 in the molecule result in a loss of activity in this assay. The
motility of fully formed male gametes, and other selected flagellated cells, is
unaffected by azadirachtin in vitro. These findings raise the possibility of
developing azadirachtin-based compounds as antimalarials with
transmission-blocking potential, as well as permitting the further study of
structure-activity relationships in these compounds.

PMID: 7980823 [PubMed - indexed for MEDLINE]

277: Indian J Exp Biol. 1994 Jul;32(7):489-91.

Anxiolytic activity of Azadirachta indica leaf extract in rats.

Jaiswal AK, Bhattacharya SK, Acharya SB.

Department of Pharmacology, Banaras Hindu University, Varanasi, India.

Putative anxiolytic activity of leaf extract of A. indica, was investigated and
compared with that of diazepam in rats using elevated plus maze and open field
behaviour test paradigms of anxiety. Doses (10, 20, 50, 100, 200, 400 and 800
mg/kg) of freshly prepared leaf extract of A. indica and diazepam (1 mg/kg) were
administered (po) once, 45 min prior to behavioural testing. Low doses (10, 20,
50, 100 and 200 mg/kg) of A. indica leaf extract produced significant
antianxiety effects both in plus maze and open field test. However, the higher
doses of leaf extract (400 and 800 mg/kg) did not show anxiolytic activity. The
effects induced by low doses (10, 20, 50, 100, 200 mg/kg) of extract were
comparable to those of induced by diazepam (1 mg/kg).

PMID: 7959927 [PubMed - indexed for MEDLINE]

278: Indian J Physiol Pharmacol. 1994 Jul;38(3):223-5.

Erratum in:
Indian J Physiol Pharmacol 1994 Oct;38(4):239.

Pharmacological effects of Azadirachta indica (neem) leaf extract on the ECG and
blood pressure of rat.

Koley KM, Lal J.

Division of Pharmacology and Toxicology, Indian Veterinary Research Institute,
Izatnagar, Bareilly.

Neem leaf alcoholic extract (NLE) was investigated for its effects on the ECG
and blood pressure of rat. Intravenous administration of NLE (100, 300 and 1000
mg/kg) resulted in initial bradycardia followed by cardiac arrhythmia in rats.
NLE produced a significant and dose-related fall in blood pressure which was
immediate, sharp and persistent. Pre-treatment with either atropine or
mepyramine failed to prevent the hypotensive effect of NLE.

PMID: 7814089 [PubMed - indexed for MEDLINE]

279: J Med Entomol. 1994 May;31(3):505-7.

Personal protection from mosquitoes (Diptera: Culicidae) by burning neem oil in

Sharma VP, Ansari MA.

Malaria Research Centre (ICMR), Delhi, India.

The repellent action of neem oil (extracted from the seeds of Azadirachta indica
A. Juss) was evaluated on mosquitoes at two villages near Delhi, India. Kerosene
lamps containing neem oil were burned in the living rooms, and mosquitoes
resting walls or attracted to human bait were collected inside rooms from 1800
to 0600 h. Neem oil (0.01-1%) mixed in kerosene reduced biting of human
volunteers and catches of mosquitoes resting on walls in the rooms. Protection
was more pronounced against Anopheles than against Culex. A 1% neem oil-kerosene
mixture may provide economical personal protection from mosquito bites.

PMID: 7914543 [PubMed - indexed for MEDLINE]

280: Cancer Lett. 1994 Apr 29;79(1):107-15.

Precursors of N-nitroso compounds in some Nigerian medicinal plants.

Atawodi SE, Spiegelhalder B.

Department of Environmental Carcinogens, German Cancer Research Center,

Twenty-seven tropical plants of medicinal importance were analysed for primary
and secondary amines by chemiluminescence detection on a Thermal Energy Analyzer
(TEA) modified for use on 'nitrogen mode' following derivatization with benzene
sulphonyl chloride (BSC) and gas chromatographic (GC) separation of their
sulphonamides. Nitrite was determined by colorimetry at 540 nm after
diazotization with sulphanilamide and coupling with
N-(1-naphthyl)ethylenediamine to form an azo dye. Nitrate was determined as
nitrite following on-line reduction by granulated cadmium. Dimethylamine in the
range of 0.5 ppm to 18.2 ppm was detected in 96% of samples, while pyrrolidine
ranged between 0.7 ppm and 12.78 ppm in 14 samples. Isobutylamine, methylamine
and ethylamine were the most ubiquitous primary amines. Largest number of
secondary amines (four) was found in Azadirachta indica (Neem) while largest
number of primary amines (six) was detected in Azadirachta indica and Tamarindus
indica (Tsamiya) which also contained the highest amount of total primary amines
(148.8 ppm). Nitrate and nitrite were seldom found in plant extracts whose pH
were generally below 7.0. These findings suggests that early exposures to
precursors of N-nitroso compounds via medicinal plants might contribute to total
risk posed by environmental carcinogens in Nigeria.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 8187049 [PubMed - indexed for MEDLINE]

281: J Ethnopharmacol. 1994 Mar;42(1):71-2.

Comment on:
J Ethnopharmacol. 1992 Jan;35(3):267-73.

Toxicology of Azadirachta indica.

Ali BH.

Publication Types:

PMID: 8046948 [PubMed - indexed for MEDLINE]

282: Mol Cell Biochem. 1994 Feb 9;131(1):87-96.

Isolation and characterization of two IgE-reactive proteins from Azadirachta
indica pollen.

Karmakar PR, Chatterjee BP.

Department of Biological Chemistry, Indian Association for the Cultivation of
Science, Jadavpur, Calcutta.

Two allergenically active components present in the Azadirachta indica whole
pollen extract have been isolated by sequential ammonium sulfate precipitation
(0-90%), DEAE-Sephadex A-50 ion-exchange chromatography followed by gel
filtration through Sephadex G-200. The allergenicity of fractionated materials
has been tested by skin prick test and ELISA inhibition which reveal that AIaI
and AIaIVb are the major allergens. Immunoblot confirms the IgE-binding activity
of the proteins. Although both fractions are found to be homogeneous by
SDS-PAGE, isoelectric focusing produces more than one isoelectric point in AIaI
(pI = 3.15, 3.3 and 3.5) and AIaIVb (pI = 6.0 and 6.2). Amino acid analyses of
the two allergens, the effect of pH on them and cross-reactivity between them
have been discussed.

PMID: 7519303 [PubMed - indexed for MEDLINE]

283: Contraception. 1993 Dec;48(6):591-6.

Studies on the contraceptive efficacy of Praneem polyherbal cream.

Garg S, Taluja V, Upadhyay SN, Talwar GP.

National Institute of Immunology, New Delhi, India.

Praneem polyherbal cream, a spermicidal formulation, has been developed at the
National Institute of Immunology, which makes use of Praneem, a purified extract
from the dried seeds of an ancient Indian plant Azadirachta indica (Neem),
extract from the pericarp of fruits of Sapindus species and quinine
hydrochloride. These ingredients have a synergistic spermicidal activity and an
optimised formula was derived. The components were made into a water-soluble
cream base prepared by using pharmaceutically acceptable base and stabilised by
addition of IP grade antioxidant and preservatives. The cream is devoid of
irritation and sensitization potential, as seen with standard Draize test on
normal and abraded skin of rabbits and by 21-day cumulative skin sensitivity in
human volunteers. The formulation was found to be safe under subacute toxicity
studies in monkeys. The formulation has shown high contraceptive efficacy in
rabbits and in monkeys after intravaginal application. The shelf-life of the
cream at room temperature is estimated to be 18 months by accelerated stability

PIP: In India, the National Institute of Immunology has developed Praneem
polyherbal cream as a vaginal spermicide. Scientists combined a purified extract
from the dried seeds of an ancient Indian plant Azadirachta indica (Neem),
extract from the pericarp of fruits of Sapindus species, and quinine
hydrochloride with a pharmaceutically acceptable base to make a water-soluble
cream base. They added IP grade antioxidant and preservatives to stabilize the
cream base. They applied the cream on a shaved or abraded part of the skin of
human volunteers and rabbits and inserted it into the vagina of Bonnet monkeys
to test for sensitivity and irritation. They studied the dissolution
characteristics of the cream after intravaginal application in the rabbits and
monkeys. They compared pregnancy rates of monkeys who received intravaginal
application of 2 ml cream every day with those of control monkeys. Praneem
polyherbal cream did not irritate the skin of the rabbits or the human
volunteers. The accelerated stability studies found the shelf-life of the cream
at room temperature to be 18 months. The cream dissolves entirely within 30
minutes in the vaginal secretions of the rabbits and 40 minutes in those of the
monkeys. Precoital application of the cream provided complete protection against
pregnancy in rabbits in the 1st 30 minutes after application. The conception
rate was acceptable at 60 minutes (7%), but thereafter it climbed to
unacceptable levels (28.6% at 90 minutes and 75% at 12 hours). The conception
rate of monkeys who received precoital application of Praneem polyherbal cream
was only 2.27%. These results suggest that Praneem polyherbal cream can protect
against pregnancy without causing irritation. Its antimicrobial properties
provide another advantage.

PMID: 8131399 [PubMed - indexed for MEDLINE]

284: J Am Mosq Control Assoc. 1993 Sep;9(3):359-60.

Mosquito repellent action of neem (Azadirachta indica) oil.

Sharma VP, Ansari MA, Razdan RK.

Malaria Research Centre, Delhi, India.

Two percent neem oil mixed in coconut oil, when applied to the exposed body
parts of human volunteers, provided complete protection for 12 h from the bites
of all anopheline species. Application of neem oil is safe and can be used for
protection from malaria in endemic countries.

PMID: 8245950 [PubMed - indexed for MEDLINE]

285: J R Soc Health. 1993 Aug;113(4):190-4.

Exploration of the frontiers of tradomedical practices: basis for development of
alternative medical healthcare services in developing countries.

Osujih M.

Rivers State College of Education, Port Harcourt, Nigeria.

The study is a brief exploration of the functions and roles of the traditional
healers in the total health care delivery system as a basis for tapping the
salient features of this age old art: for the purpose of refining, and
establishing it as an alternative medical health-care service. The investigation
is considered relevant particularly in the developing countries where, in
addition to the dearth of orthodox medical services, institutions and personnel,
it is relatively cheaper, socio-culturally accessible and acceptable. Refining
and developing some aspects of the traditional healers' services will serve the
interest of the health consumers whose main concern is with service and not the
source. Furthermore, it is hoped that the study will stimulate purposeful
discussions on the need for an unbiased examination of the materials, methods
and techniques of the traditional healers including, eventually, compiling a
native pharmacopoeia. A more comprehensive account of the traditional healers
contributions to the battle against diseases and maintenance of health and well
being is envisaged.

PIP: In traditional healing, practitioners use barks, leaves, nuts, fruit juices
and roots, and parts of domestic animals. They practice their craft mostly in
Africa, Asia, and other Third World countries, and they are variously called
juju priests, diviners, herbalists, and witch doctors. Cases of achievements in
their contributions to preventive and curative health have been documented. In
Nigeria, clients regularly patronize both orthodox and traditional medical
practitioners. Their remedies include healing the bite of the very poisonous
carpet viper, chronic bronchitis, peptic ulcer, and heart problems, as well as
performing uvulectomy and tonsillectomy. Quinine, the cure for malaria, was
originally the ritual medicine of the Incas of Peru. It was confirmed that
Azadirachta Indica (Meliaceae), the neem tree, used against malaria in Nigeria,
India, and Asia, had a potent antiplasmodial activity. The plant Streblus
asper, Linn (Shakhotoha Siora) is well known in Indian Ayurvedic medicine to
treat fever, filariasis, dysentery, and diarrhea. The alkaloids derived from
the Madagascan periwinkle Catharanthus roseus (Apocynaceae), used in a West
Indian remedy for diabetes mellitus, have antitumor activity. The drug
Maytensine, obtained from Mytenus ovatus Loes (Celastraceae), was found to be a
powerful antitumor agent in animals. Tea made from the leaves of Osyris
wightiana stimulated the flow of breast milk and also acted as a labor-inducing
agent. Saponaria officinalis and Enterobbium cyclocarpum are both used in Egypt
and Tanzania as spermicide contraceptives. A 1985 survey in Cross River State,
Nigeria, demonstrated that 165 (61%) of respondents went to traditional healers
for treatment. Part of their continued popularity is the person-centered
approach that is virtually lacking in orthodox hospitals, although this
humanistic approach to therapy is gradually gaining inroads into Western medical
education. The services of both kinds of medicine could be harmonized by
open-minded appraisal, identification of positive aspects, and acceptance of
their complimentary nature.

Publication Types:
Comparative Study

PMID: 8410912 [PubMed - indexed for MEDLINE]

286: J Androl. 1993 Jul-Aug;14(4):275-81.

Antifertility effects of neem (Azadirachta indica) oil in male rats by single
intra-vas administration: an alternate approach to vasectomy.

Upadhyay SN, Dhawan S, Talwar GP.

National Institute of Immunology, New Delhi, India.

An alternate approach to vasectomy for long-term male contraception following a
single intra-vas application of a traditional plant (Azadirachta indica) product
having immunomodulatory properties is described. Male Wistar rats of proven
fertility were given a single dose (50 microliters) of neem oil in the lumen of
the vas deferens on each side; control animals received the same volume of
peanut oil. Animals were put on continuous mating 4 weeks after the treatment,
with females of proven fertility. While the control animals impregnated the
female partners, all males treated with neem oil remained infertile throughout
the 8 months of observation period. Epididymal and vas histology were normal
without any inflammatory changes or obstruction. The intra-vas administration of
neem oil resulted in a block of spermatogenesis without affecting testosterone
production; the seminiferous tubules, although reduced in diameter, appeared
normal and contained mostly early spermatogenic cells. No anti-sperm antibody
could be detected in the serum. Unilateral administration of neem oil in the vas
resulted in a significant reduction of testicular size and spermatogenic block
only on the side of application; the draining lymph node cells of the treated
side also showed enhanced proliferative response to in vitro mitogen challenge.
These results indicate that the testicular effects following intra-vas
application of neem oil may possibly be mediated by a local immune mechanism.

Publication Types:
Comparative Study

PMID: 8226307 [PubMed - indexed for MEDLINE]

287: Food Chem Toxicol. 1993 Apr;31(4):297-301.

Toxicological studies on debitterized Neem oil (Azadirachta indica).

Chinnasamy N, Harishankar N, Kumar PU, Rukmini C.

National Institute of Nutrition, Indian Council of Medical Research,
Jamai-Osmania, Hyderabad.

Azadirachta indica, popularly known as 'Neem' in India, is widely grown all over
the tropics. The seed contains 45% oil and is a minor oil of considerable
potential. Neem oil is bitter and inedible. Recently, a method has been
developed to completely remove the bitter and odoriferous principles and leave a
bitterless, odourless and colourless oil. The nutritional and chemical
evaluation of debitterized neem oil (NO) was reported earlier (C. Rukmini, Food
Chemistry 1987, 26, 119). We report here a three-generation study, carried out
according to WHO/FDA protocol in groups of 15 male and 15 female rats fed a diet
containing 10% NO or groundnut oil (GNO). Reproductive toxicology was monitored
for three generations. The results obtained in both the matings in all the three
generations did not show any adverse effects on the reproductive parameters
studied in rats fed NO and were similar to those observed in rats fed GNO. The
mean organ weights and the histopathological evaluation of all the organs were
similar to those of the control (GNO-fed) rats. A mutagenicity test of NO was
also found to be negative in Ames test as reported earlier (K. Polasa and C.
Rukmini, Food and Chemical Toxicology 1987, 25, 763). These studies indicate
that NO devoid of all the bitter and odoriferous principles, may be recommended
as safe for consumption by humans.

PMID: 8477918 [PubMed - indexed for MEDLINE]

288: Appl Parasitol. 1993 Feb;34(1):63-8.

Toxicity of Azadirachta indica to freshwater snails and fish, with reference to
the physicochemical factor effect on potency.

Osuala FO, Okwuosa VN.

Department of Biological Science, River State University of Science &
Technology, Port-Harcourt.

A preliminary crude screening of plants in Jos Metropolis showed that at a
concentration of 100 mg/l-1 the stem bark extract of the Neem plant Azadirachta
indica caused a 100 percent mortality when tested against three common snail
intermediate host species, Biomphalaria pfeifferi, Bulinus truncatus, and
Lymnaea natalensis after 24 hours exposure. Toxicity test with freeze-dried
aqueous extract of the plant gave 96 hours LC50 values of 19.00 mg/l-1 (p >
0.05), 10.96 mg/l-1 (p > 0.05) and 15.13 mg/l-1 (p > 0.05) against B. pfeifferi,
B. truncatus and L. natalensis, respectively. When a similar test was carried
out on fish, Aphyosemon giardneri a 96 hour LC50 of 15.1 mg/l-1 was recorded.
Extraction with alcohol, increase in temperature within the optimal range,
increase in acidity of aquatic medium and cold storage improved the potency of
the extract while boiling and room storage reduced it.

PMID: 8508220 [PubMed - indexed for MEDLINE]

289: Afr J Med Med Sci. 1992 Dec;21(2):39-46.

"Antimalarial" medicinal plants and their impact on cell populations in various
organs of mice.

Agomo PU, Idigo JC, Afolabi BM.

National Institute for Medical Research, Yaba, Lagos.

We have investigated the effects of leaf and bark decoctions of Ocimum
gratissimum, Azadirachta indica, Morinda lucida and Enantia chlorantha on (a)
the course of Plasmodium yoelii nigeriensis malaria (b) reticulocyte and
haematocrit values and (c) nucleated cell numbers in the spleen, bone marrow,
peritoneum, liver and peripheral blood of Swiss albino mice. Results obtained
showed that normal mice infected with the parasite (10(4)/mouse) suffered
fulminant parasitaemia which resulted in death, 7-10 days later. All infected
mice treated with chloroquine survived. On the other hand all infected mice
treated with the medicinal plants exhibited varying percentages of
chemosuppression of early parasitaemia which did not lead to their survival. The
total number of nucleated cells in the liver, spleen and peripheral blood of
malaria-infected mice increased enormously before the animals died. Such
increases were maintained in other groups of mice treated with the medicinal
plants. In the non-infected mice, O.gratissimum and E. chlorantha administration
increased the number of nucleated cells in the spleen, liver and peripheral
blood. Chloroquine on the other hand decreased the number of nucleated cells in
both the malaria-infected and un-infected mice. There was also a decrease in
reticulocyte numbers in the blood of normal mice injected with chloroquine.
Conversely reticulocyte numbers increased in normal mice administered with some
medicinal plants. Acute and chronic toxicity tests revealed that some of the
medicinal plants were much more toxic than others.(ABSTRACT TRUNCATED AT 250

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 1308080 [PubMed - indexed for MEDLINE]

290: Indian J Exp Biol. 1992 Dec;30(12):1170-5.

Effects of Azadirachta indica A Juss on some biochemical, immunological and
visceral parameters in normal and stressed rats.

Sen P, Mediratta PK, Ray A.

Department of Pharmacology, University College of Medical Sciences, Shahdara,
Delhi, India.

Effects of A. indica (AI) were evaluated on some biochemical, immunological and
visceral parameters in normal and stress rats. AI (100 mg/kg) lowered blood
glucose, triglyceride and SGOT levels in normal rats, and attenuated
stress-induced elevations of cholesterol and urea levels. In rats immunized with
SRBC, AI enhanced the humoral antibody response to the antigen. Further, AI
facilitated the footpad thickness response to SRBC in sensitized mice and also
enhanced leucocyte migration in immunized rats. In stressed rats, AI
significantly attenuated the stress-induced (a) suppression of humoral immune
response and (b) gastric ulcerogenesis. These results are discussed in light of
the possible mechanisms involved in the effects of AI in normal and stressful

PMID: 1294481 [PubMed - indexed for MEDLINE]

291: Med Vet Entomol. 1992 Oct;6(4):318-24.

Evaluation of neem, Azadirachta indica, with and without water management, for
the control of culicine mosquito larvae in rice-fields.

Rao DR, Reuben R, Venugopal MS, Nagasampagi BA, Schmutterer H.

Centre for Research in Medical Entomology, Satya Sai Nagar, Madurai.

Applications of neem, Azadirachta indica (Meliaceae), to rice-fields were
evaluated with the dual objective of controlling the culicine mosquito vectors
of Japanese encephalitis virus (JEV) and enhancing the grain yield. Since crude
neem products deteriorate under improper storage conditions, a laboratory
bioassay was developed to screen neem cake powder against mosquito larvae, Culex
quinquefasciatus. Only samples of neem giving over 90% bioassay mortality were
used in field trials. When good quality neem cake powder was applied at the dose
of 500 kg/ha, either alone or coated over urea, there was a striking reduction
in the abundance of late instar culicine larvae and pupae. Only fourteen pupae
were obtained over a period of 13 weeks in neem cake powder treated plots, and
four in those treated with neem coated urea, compared with 101 in control plots.
Both treatments were significantly less than the control, but on par with one
another. In another field trial, neem cake coated urea was tested at 500 and 250
kg neem/ha in combination with water management practices. No reduction in
efficacy was noted at the lower dose. Larval abundance in plots under water
management alone did not differ significantly from the controls, but was
significantly reduced when water management was combined with neem products. Two
stable formulations, 'Neemrich-I' (lipid rich) and 'Neemrich-II' (azadirachtin
rich), also gave good suppression of immature culicines. All the treatments with
neem also gave higher grain yield than the control.(ABSTRACT TRUNCATED AT 250

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 1463896 [PubMed - indexed for MEDLINE]

292: Int J Immunopharmacol. 1992 Oct;14(7):1187-93.

Immunomodulatory effects of neem (Azadirachta indica) oil.

Upadhyay SN, Dhawan S, Garg S, Talwar GP.

National Institute of Immunology, New Delhi, India.

Immunomodulatory effects of neem oil were studied in mice. The animals were
treated intraperitoneally (i.p.) with neem oil; control animals received the
emulsifying agent with or without peanut oil. Peritoneal lavage, collected on
subsequent days, showed a maximum number of leukocytic cells on day 3 following
treatment with neem oil; peritoneal macrophages exhibited enhanced phagocytic
activity and expression of MHC class-II antigens. Neem oil treatment also
induced the production of gamma interferon. Spleen cells of neem oil-treated
animals showed a significantly higher lymphocyte proliferative response to in
vitro challenge with Con A or tetanus toxoid (TT) than that of the controls.
Pre-treatment with neem oil, however, did not augment the anti-TT antibody
response. The results of this study indicate that neem oil acts as a
non-specific immunostimulant and that it selectively activates the cell-mediated
immune (CMI) mechanisms to elicit an enhanced response to subsequent mitogenic
or antigenic challenge.

Publication Types:
In Vitro

PMID: 1452404 [PubMed - indexed for MEDLINE]

293: Indian J Exp Biol. 1992 Aug;30(8):738-40.

Hepatoprotective activity of Azadirachta indica leaves on paracetamol induced
hepatic damage in rats.

Chattopadhyay RR, Sarkar SK, Ganguly S, Banerjee RN, Basu TK, Mukherjee A.

Biometry Research Unit Indian Statistical Institute, Calcutta.

Effect of A. indica leaf extract on serum enzyme levels (glutamate oxaloacetate
transaminase, glutamate pyruvate transaminase, acid phosphatase and alkaline
phosphatase) elevated by paracetamol in rats was studied with a view to observe
any possible hepatoprotective effect of this plant. It was interesting to
observe that serum enzyme levels were much elevated in paracetamol induced
animals than in those receiving a combination of paracetamol and lead extract.
It is stipulated that the extract treated group was protected from hepatic cell
damage caused by paracetamol induction. The findings were further confirmed by
histopathological study of liver.

PMID: 1459654 [PubMed - indexed for MEDLINE]

294: Vet Hum Toxicol. 1992 Jun;34(3):221-4.

Experimental Azadirachta indica toxicosis in chicks.

Ibrahim IA, Omer SA, Ibrahim FH, Khalid SA, Adam SE.

Faculty of Veterinary Science, University of Khartoum, Sudan.

Brown Hisex chicks were fed Azadirachta indica ripe fruit at 2, 5 or 10% of
basic diet from their 7th to 35th d of age. Decreased body weight gain and
efficiency of feed utilization and hepatonephropathy were most severe in chicks
fed the 10% A indica diet. These changes were accompanied by anemia and
increases in LDH, GOT and ALP activities and uric acid concentration and by
decreased serum total protein. Hepatocytes and renal tubular cells did not
completely revert to normal 2 w after removal from the test diets.

PMID: 1609490 [PubMed - indexed for MEDLINE]

295: Jpn J Med Sci Biol. 1992 Jun;45(3):137-50.

Mitochondrial malate dehydrogenase and malic enzyme of a filarial worm Setaria
digitata: some properties and effects of drugs and herbal extracts.

Banu MJ, Nellaiappan K, Dhandayuthapani S.

Department of Zoology, University of Madras, India.

Mitochondrial malate dehydrogenase (mMDH) and malic enzyme (mME) of a filarial
worm Setaria digitata were studied. mMDH exhibited the highest activities in the
oxidation and reduction reactions at pH 9.5 and pH 6.2, respectively, while mME
did so in the malate decarboxylation reaction at pH 6.8. mME showed no
detectable activity on the pyruvate carboxylation direction. The Km values for
malate (1.7 mM) and oxaloacetate (0.17 mM) and the ratio of Vmax oxidation: Vmax
reduction (2.73) tend to favor the oxaloacetate reduction by mMDH. mME showed a
relatively high Km value of 8.3 mM, for malate decarboxylation. A drug,
diethylcarbamazine citrate (DEC-C), did not change appreciably the activity of
either mMDH or mME, while filarin (a drug of herbal origin) effectively
inhibited mMDH. The leaf extracts of Ocimum sanctum, Lawsonia inermis and
Calotropis gigantea and leaf and flower extracts of Azadirachta indica were,
however, found to inhibit both mMDH and mME.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 1291764 [PubMed - indexed for MEDLINE]

296: J Nat Prod. 1992 Mar;55(3):303-10.

Constituents of Azadirachta indica: isolation and structure elucidation of a new
antibacterial tetranortriterpenoid, mahmoodin, and a new protolimonoid,

Siddiqui S, Faizi S, Siddiqui BS, Ghiasuddin.

H.E.J. Research Institute of Chemistry, University of Karachi, Pakistan.

Mahmoodin [1], a new limonoid, has been isolated from Azadirachta indica (neem)
oil, along with seven known tetranortriterpenoids, azadirone, epoxyazadiradione,
nimbin, gedunin, azadiradione, deacetylnimbin, and 17-hydroxyazadiradione. A new
protolimonoid, naheedin [3], has been obtained from the neem fruits along with
azadirachtol. Their structures have been elucidated through chemical and
spectral analyses including 2D nmr studies. The absolute configuration of 1 was
established by comparison of its cd spectrum with those of the known
tetranortriterpenoids. Mahmoodin showed significant antibacterial activity
against various Gram-positive and Gram-negative organisms. Four hydrocarbons,
icosane, docosane, 2-methyltricosane, and docosene, have also been identified by
gc-ms of the EtOH extract of the fruit coats. Only docosane has earlier been
reported from neem, while the remaining three are unreported from this plant.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 1593280 [PubMed - indexed for MEDLINE]

297: J Ethnopharmacol. 1992 Jan;35(3):267-73.

Comment in:
J Ethnopharmacol. 1994 Mar;42(1):71-2.

On the toxicology of Azadirachta indica leaves.

Ibrahim IA, Khalid SA, Omer SA, Adam SE.

Department of Veterinary Medicine, Pharmacology and Toxicology, University of
Khartoum, Sudan.

Brown Hisex chicks were fed diets containing 2% and 5% Azadirachta indica leaf
from their 7th to 35th day of age. Thereafter, the chicks were fed control diet
for 2 weeks. A depression in body weight gain and efficiency of feed utilization
was observed in chicks fed A. indica leaf when compared with the control. The
main clinicopathological changes were increases in lactic dehydrogenase,
glutamic oxaloacetic transaminase and alkaline phosphatase activities and uric
acid and bilirubin concentrations and decreases in the total protein levels in
serum. Changes in the values of erythrocyte count, haemoglobin concentration,
packed cell volume, mean corpuscular volume and mean corpuscular haemoglobin
were remarkable and associated with yellow discoloration on the legs and combs
and hepatonephropathy. Tissue recovery was incomplete 2 weeks after removal from
the experimental diets.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 1548899 [PubMed - indexed for MEDLINE]

298: Trop Geogr Med. 1992 Jan;44(1-2):178-81.

The use and efficacy of Azadirachta indica ADR ('Neem') and Curcuma longa
('Turmeric') in scabies. A pilot study.

Charles V, Charles SX.

Medical and Cancer Research and Treatment Centre, Nagercoil, India.

In the Ayurvedha and Sidha system of medicine (Indian system of medicine)
Azadirachta indica ADR ('Neem') and Curcuma longa ('Turmeric') has been used for
healing chronic ulcers and scabies. The 'Neem' and 'Turmeric' was used as a
paste for the treatment of scabies in 814 people. In 97% of cases cure was
obtained within 3 to 15 days of treatment. We find that this is a very cheap,
easily available, effective and acceptable mode of treatment for the villagers
in the developing countries. We have noticed no toxic or adverse reaction so
far. However, further research is needed.

PMID: 1496714 [PubMed - indexed for MEDLINE]

299: Mem Inst Oswaldo Cruz. 1992;87 Suppl 5:69-72.

Effects of azadirachtin on Rhodnius prolixus: immunity and Trypanosoma

de Azambuja P, Garcia ES.

Departamento de Bioquimica e Biologia Molecular, Instituto Oswaldo Cruz, Rio de
Janeiro, Brasil.

The effects of azadirachtin, a tetranortriterpenoid from the neem tree
Azadirachta indica J., on both immunity and Trypanosoma cruzi interaction within
Rhodnius prolixus and other triatomines, were presented. Given through a blood
meal, azadirachtin affected the immune reactivity as shown by a significant
reduction in numbers of hemocytes and consequently nodule formation following
challenge with Enterobacter cloacae beta 12, reduction in ability to produce
antibacterial activities in the hemolymph when injected with bacteria, and
decreased ability to destroy the infection caused by inoculation of E. cloacae
cells. A single dose of azadirachtin was able to block the development of T.
cruzi in R. prolixus if given through the meal at different intervals, together
with, before or after parasite infection. Similarly, these results were observed
with different triatomine species and different strains of T. cruzi.
Azadirachtin induced a permanent resistance of the vector against reinfection
with T. cruzi. The significance of these data is discussed in relation to the
general mode of azadirachtin action in insects.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 1342719 [PubMed - indexed for MEDLINE]

300: Indian J Physiol Pharmacol. 1991 Oct;35(4):278-80.

Neem oil--a fertility controlling agent in rhesus monkey.

Bardhan J, Riar SS, Sawhney RC, Kain AK, Thomas P, Ilavazhagan G.

Defence Institute of Physiology and Allied Sciences, Delhi Cantt.

Neem oil, an oil extracted from the seeds of Azadirachta indica has been found
to act as a good spermicidal agent. Pre and post coital application of the oil
intravaginally prevented pregnancy in rhesus monkey.

PMID: 1812107 [PubMed - indexed for MEDLINE]

301: J Ethnopharmacol. 1991 Oct;35(1):1-24.

Ethnopharmacognostical survey of Azadirachta indica A. Juss (Meliaceae).

van der Nat JM, van der Sluis WG, de Silva KT, Labadie RP.

Section of Pharmacognosy, Faculty of Pharmacy, University of Utrecht, The

Literature data on respectively botany, chemistry, ethnopharmacology,
pharmacology and toxicology of Azadirachta indica A. Juss. (Meliaceae) are
reviewed and evaluated. In traditional literature, preparations of the tree are
claimed to be vulnerable in wide spectrum of diseases. Especially for
inflammation-related diseases a good correlation is found with the results of
recent experimental investigations. In addition, a variety of other biological
activities are reported. Most frequently the effects can be attributed to
compounds representing the structural classes of the limonoids, phenolics and
macromolecules. Reported toxicity of preparations and isolated compounds are
low, except for the seed oil. In conclusion, A. indica can be regarded as a
valuable plant source for the rationalisation of its use in traditional medicine
and for modern drug development.

Publication Types:

PMID: 1753794 [PubMed - indexed for MEDLINE]

302: Planta Med. 1991 Feb;57(1):65-8.

Activity-guided isolation and identification of Azadirachta indica bark extract
constituents which specifically inhibit chemiluminescence production by
activated human polymorphonuclear leukocytes.

van der Nat JM, van der Sluis WG, 't Hart LA, Van Dijk H, de Silva KT, Labadie

Section of Pharmacognosy, Faculty of Pharmacy, State University of Utrecht, The

The A. indica crude aqueous bark extract inhibits the generation of
chemiluminescence by activated human polymorphonuclear leukocytes (PMN). Guided
by this activity the responsible compounds were purified by extraction with
different organic solvents and HPLC. Gallic acid, (+)-gallocatechin,
(-)-epicatechin, and (as a 2:1 mixture) (+)-catechin and epigallocatechin were
isolated and identified by means of HPLC, TLC, MS, 1H-NMR, UV, and CD data.
Commercial samples of gallic acid, (+)-catechin and (-)-epicatechin showed the
same effects. To our knowledge the identified catechins have never been
described as constituents of A. indica.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 2062961 [PubMed - indexed for MEDLINE]

303: Pak J Pharm Sci. 1991 Jan;4(1):71-6.

Toxicity and IGR effect of two new neem products against Aedes aegypti (PCSIR

Naqvi SN, Ahmed SO, Mohammad FA.

Department of Zoology, University of Karachi, Karachi-75270, Pakistan.

Crude extract and isolated compounds from neem, Azadirachta indica and Melia
azedarach (Meliaceae) are being tested in various countries. The present study
deals with the effect of two new compounds and their parent fraction from the
fresh winter neem leaves, isolated by Siddiqui et. al., 1986. The LC50 of NFD is
0.58 ppm, nimocinolide 0.625 ppm and isonimocinolide 0.47 ppm. Abnormal larvae,
pupae and intermediates were also found.

PMID: 16414684 [PubMed]

304: Mem Inst Oswaldo Cruz. 1991;86 Suppl 2:107-11.

Effects of azadirachtin in Rhodnius prolixus: data and hypotheses.

Garcia ES, Gonzales MS, Azambuja P.

Instituto Oswaldo Cruz, Departamento de Bioquimica e Biologia Molecular, Rio de
Janeiro, Brasil.

The effects of azadirachtin A, a tetranortriterpenoid from the neem tree
Azadirachta indica J., on both development and interaction between Trypanosoma
cruzi, the causative agent of Chagas' disease, and its vector Rhodnius prolixus
were studied. Given through a blood meal, a dose-response relationship of
azadirachtin was established using antifeedant effect and ecdysis inhibition as
effective parameters. A single dose of azadirachtin A was able to block the
onset of mitosis in the epidermis and ecdysteroid titers in the hemolymph,
determined by radioimmuneassay, were too low for an induction of ecdysis. The
survival of T. cruzi was also studied in R. prolixus treated with the drug. If
the trypomastigotes were fed in presence of azadirachtin A the number of
parasites drastically decreased. If the drug was applied after infection of the
bug with T. cruzi, the parasite was still abolished from the gut. If the insect
was pretreated with azadirachtin A before infection the same observation was
obtained. A single dose of azadirachtin A was enough for a permanent resistance
of the insect host against its reinfection with T. cruzi and for blocking the
ecdysis for a long time. The effects of azadirachtin A on the hormonal balance
of the host and growth inhibition of the parasite will be discussed on the basis
of the present results.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 1841982 [PubMed - indexed for MEDLINE]

305: Proc Biol Sci. 1990 Dec 22;242(1305):175-9.

Antifertility effects of neem (Azadirachta indica) oil by single intrauterine
administration: a novel method for contraception.

Upadhyay SN, Kaushic C, Talwar GP.

National Institute of Immunology, New Delhi, India.

A novel use of neem (Azadirachta indica) oil, a traditional plant product, for
long-term and reversible blocking of fertility after a single intrauterine
application is described. Female Wistar rats of proven fertility were given a
single dose (100 microliters) of neem oil by intrauterine route; control animals
received the same volume of peanut oil. Whereas all control animals became
pregnant and delivered normal litters, the rats treated with neem oil remained
infertile for variable periods ranging from 107 to 180 days even after repeated
matings with males of proven fertility. The block in fertility was, however,
reversible as half of the animals regained fertility and delivered normal
litters by five months after treatment, without any apparent teratogenic
effects. Unilateral administration of neem oil in the uterus blocked pregnancy
only on the side of application whereas the contralateral uterine horn treated
with peanut oil had normally developing foetuses; no sign of implantation or
foetal resorption was noted in the neem-oil-treated horn. The ovaries on both
sides had 4-6 corpora lutea indicating no effect of treatment on ovarian
functions. The animals treated with neem oil showed a significant leukocytic
infiltration in the uterine epithelium between days 3 and 5 post coitum, i.e.
during the pre-implantation period. Intrauterine application of neem oil appears
to induce a pre-implantation block in fertility; the possible mechanisms of the
antifertility action are discussed.

PMID: 1983033 [PubMed - indexed for MEDLINE]

306: Indian J Exp Biol. 1990 Aug;28(8):714-6.

Antifertility effects of leaf extracts of some plants in male rats.

Choudhary DN, Singh JN, Verma SK, Singh BP.

University Department of Botany, Bhagalpur University, India.

Ethanolic leaf extracts of different local folklore plants (Azadirachta indica,
Beaumontia grandiflora, Chordia dichotoma, Casiarea tomentosa, Diospyros
embryopteris, Milletia auriculata and Melia azedarach) were investigated for
antifertility effects on male rats in oral doses of 100 mg/kg daily for 21 days.
Though, none of these extracts interfered with spermatogenesis,
anti-implantational and abortifacient effects were observed in females mated by
the males fed with leaf extracts of A. indica and C. dichotoma. Leaf extract of
B. grandiflora besides having anti-implantational and abortifacient effects, had
luteolytic effects. Abolition of libido in 100% males by leaf extracts of D.
embryopteris and M. azedarach and in 60% of males by extract of C. tomentosa
preclude these plants for antifertility use.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 2253961 [PubMed - indexed for MEDLINE]

307: Planta Med. 1990 Feb;56(1):84-6.

Tricyclic Diterpenes from the Stem Bark of Azadirachta indica.

Ara I, Siddiqui BS, Faizi S, Siddiqui S.

H.E.J. Research Institute of Chemistry, University of Karachi, Karachi-32,

Two new diterpenoids, margosone and margosolone, have been isolated from the
stem bark of AZADIRACHTA INDICA A. Juss (neem) and their structures established
as 12,13-dihydroxy-14-isoporpylpodocarpa-8,11,13-trien-7-one and
13-hydroxy-12-methoxypodocarpa-8,11,13-trien-7-one, respectively, through
chemical and spectroscopic studies.

PMID: 17221373 [PubMed - in process]

308: Annu Rev Entomol. 1990;35:271-97.

Properties and potential of natural pesticides from the neem tree, Azadirachta

Schmutterer H.

Institut fur Phytopathologie und Angewandte Zoologie, Universitat Giessen,
Federal Republic of Germany.

Publication Types:

PMID: 2405771 [PubMed - indexed for MEDLINE]

309: Ciba Found Symp. 1990;154:80-7; discussion 87-98.

Synthesis of antifeedants for insects: novel behaviour-modifying chemicals from

Ley SV.

Department of Chemistry, Imperial College of Science, Technology and Medicine,
London, UK.

The need to protect our food supply from predatory insect attack using more
ecologically acceptable methods has led to a rapidly growing interest in
behavior-modifying chemicals from natural sources. Compounds which deter insects
from feeding (antifeedants) are attracting special attention owing to their
potential use in integrated pest control management systems. We have been
studying the synthesis of plant-derived compounds that display antifeedant
properties. The aim of the work is to understand more precisely the feeding
mechanisms of insects at a molecular level so as ultimately to be able to design
simpler compounds capable of mimicking the activity of the natural products. Our
synthetic studies on the sesquiterpenoid antifeedants, polygodial and
warburganal, and on the diterpenoid clerodane, ajurgarin I, have shown the
promise of this approach. Current effort is directed towards structure-activity
studies and synthesis of the extraordinarily potent antifeedant and
growth-disrupting agent azadirachtin, isolated from the Neem tree, Azadirachta
indica (A. Juss). This work has led to the correct structure assignment for
azadirachtin and afforded many compounds for biological evaluation. It is of
special significance that incorporation of the hydroxydihydrofuran portion of
azadirachtin in a simple model system formed a compound with antifeedant
activity comparable to that of the natural product.

Publication Types:

PMID: 2086043 [PubMed - indexed for MEDLINE]

310: J Ethnopharmacol. 1989 Nov;27(1-2):15-24.

Characterization of anti-complement compounds from Azadirachta indica.

van der Nat JM, Hart LA, van der Sluis WG, van Dijk H, van den Berg AJ, de Silva
KT, Labadie RP.

Faculty of Pharmacy, Medical Faculty, State University of Utrecht, The

The crude aqueous extract of Azadirachta indica bark possesses an inhibitory
activity on both classical (CP) and alternative pathway (AP) activation of human
complement. Purification of the compounds with the guidance of the AP-inhibitory
activity involved extraction with methanol, dialysis, ion-exchange procedures
and gel-permeation chromatography. This sequence yielded two polymers, NB-I and
NB-II, one a highly active compound with a relatively low molecular weight
(NB-II) and the other a less active compound with a high molecular weight
(NB-I). The polymers were characterized by using colour reactions, TLC, GLC and
HPLC after hydrolysis and gel-permeation chromatography as peptidoglycans. The
carbohydrate part consisted predominantly of glucose. Arabinose, galactose and
mannose were present in minor amounts (NB-II) or only as traces (NB-I). Protein
was present for 5.5% in NB-I and for 9.8% in NB-II.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 2615417 [PubMed - indexed for MEDLINE]

311: J Nat Prod. 1989 Nov-Dec;52(6):1246-51.

Spectroscopic and biological investigation of nimbolide and 28-deoxonimbolide
from Azadirachta indica.

Kigodi PG, Blasko G, Thebtaranonth Y, Pezzuto JM, Cordell GA.

Program for Collaborative Research in the Pharmaceutical Sciences, University of
Illinois, College of Pharmacy, Chicago 60680.

The reisolation of nimbolide [1] from Azadirachta indica of Tanzanian origin and
the isolation and structure elucidation of a new limonoid, 28-deoxonimbolide
[2], from the same plant source are reported. For the first time, unambiguous
1H- and 13C-nmr assignments of compounds 1 and 2 are presented, as well as their
in vitro cytotoxic activity against human tumor cell lines.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

PMID: 2614419 [PubMed - indexed for MEDLINE]

312: J Econ Entomol. 1989 Oct;82(5):1375-8.

Azadirachtin as a larvicide against the horn fly, stable fly, and house fly
(Diptera: Muscidae).

Miller JA, Chamberlain WF.

Effects of azadirachtin, a triterpenoid extracted from neem seed, Azadirachta
indica A. Juss., were similar to those of insect growth regulators against the
immature stages of the born fly, Haematobia irritans (L.), the stable fly,
Stomoxys calcitrans (L.), and the house fly, Musca domestica L. When an
ethanolic extract of ground seed was blended into cow manure, LC50 and LC90's
for larval horn flies were 0.096 and 0.133 ppm azadirachtin, respectively. An
emulsifiable concentrate (EC) had an LC50 for larval horn flies of 0.151 ppm and
an LC90 of 0.268 ppm. For larval stable flies, the EC formulation had an LC50 of
7.7 ppm and an LC90 of 18.7 ppm azadirachtin in manure. Against larval house
flies, the LC50 and LC90 were 10.5 and 20.2 ppm, respectively. When the EC
formulation was administered orally to cattle at a rate of greater than or equal
to 0.03 mg azadirachtin per kg of body weight per day or when ground neem seed
was given as a daily supplement of greater than or equal to 10 mg seed per kg
body weight, horn fly development in the manure was almost completely inhibited.
In contrast, ground seed mixed in cattle feed at the rate of 100-400 mg seed per
kg of body weight per day caused less than 50% inhibition of stable flies in the

PMID: 2600264 [PubMed - indexed for MEDLINE]

313: J Nat Prod. 1989 Sep-Oct;52(5):922-6.

Isolation and characterization of an antimalarial agent of the neem tree
Azadirachta indica.

Khalid SA, Duddeck H, Gonzalez-Sierra M.

Department of Pharmacognosy, Faculty of Pharmacy, University of Khartoum, Sudan.

The isolation and structure elucidation of gedunin [1], the antimalarial agent
of Azadirachta indica, are reported. Its 1H- and 13C-nmr spectra were assigned
by using one- and two-dimensional nmr spectroscopy, especially homonuclear and
heteronuclear COSY, nOe difference, and COLOC experiments.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 2607354 [PubMed - indexed for MEDLINE]

314: Planta Med. 1989 Aug;55(4):339-48.

An ethnopharmacognostic approach to the search for immunomodulators of plant

Labadie RP, van der Nat JM, Simons JM, Kroes BH, Kosasi S, van den Berg AJ, t'
Hart LA, van der Sluis WG, Abeysekera A, Bamunuarachchi A, et al.

The search for immunomodulating plant constituents through basic and field
inquiries into the literature and practices of traditional Indian medicine is
treated. The strategy of data collecting proceeds through aspects of an
ethnobotanical, an ethnopharmaceutical, an ethnopharmacological, and an
ethnomedical nature. In the experimental immunopharmacognostic phase,
immunomodulatory compounds are isolated and purified through action-guided
fractionation procedures. The results described here refer to activities found
on human complement activation and on PMN leucocytes activation. The
immunomodulating plant compounds included in this report were isolated from
Azadirachta indica bark, Woodfordia fructicosa flowers, Picrorhiza kurroa roots,
and Jatropha multifida latex.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 2682699 [PubMed - indexed for MEDLINE]

315: J Ethnopharmacol. 1989 May;25(3):315-38.

[Anti-infective phytotherapies of the tree-savannah, Senegal (occidental
Africa). III: A review of phytochemical substances and the antimicrobial
activity of 43 species]

[Article in French]

Le Grand A.

Department of Pharmacognosy, University of Leyden, The Netherlands.

A review has been made of the ethnobotanical and pharmacological data of 43
medicinal plants of the tree-savannah used by the Diola against infectious
diseases. The traditional use of ten plants can be explained by
pharmacologically active principles: Adansonia digitata, Azadirachta indica,
Carica papaya, Cassia tora, Fagara leprieurii, Guiera senegalensis, Khaya
senegalensis, Mangifera indica, Psidium guajava and Voacanga africana. Four of
these herbs are recommended for use in Primary Health Care. The therapeutic
value of the other plants discussed is not absolutely clear. It is, however,
obvious that herbal medicine has a large potential, which is still
insufficiently explored, for utilization in Primary Health Care.

Publication Types:
English Abstract

PMID: 2664354 [PubMed - indexed for MEDLINE]

316: Indian J Malariol. 1988 Dec;25(2):67-72.

Evaluation of four azadirachtin rich fractions from neem, Azadirachta indica A.
Juss (family: meliaceae) as mosquito larvicides.

Rao DR, Reuben R, Gitanjali Y, Srimannarayana G.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 2908329 [PubMed - indexed for MEDLINE]

317: Planta Med. 1988 Oct;54(5):457-9.

Non-Terpenoidal Constituents from Azadirachta indica.

Siddiqui S, Mahmood T, Siddiqui BS, Faizi S.

H. E. J. Research Institute of Chemistry, University of Karachi, Karachi-32,

Studies on the acidic fraction of the fresh, uncrushed twigs of AZADIRACHTA
INDICA JUSS (Meliaceae) (Neem) have resulted in the isolation and structure
elucidation of one new and three unreported isocoumarins along with two
unreported coumarins. The petroleum ether extract of the fresh leaves yielded a
hydrocarbon fraction, the GC-MS of which led to the identification of eight
saturated hydrocarbons. Fatty acid compositions of leaves, twigs, and fruits of
neem have also been determined.

PMID: 17265315 [PubMed - in process]

318: Indian J Med Res. 1988 Oct;88:339-42.

Mechanism of antifertility action of neem oil.

Riar SS, Bardhan J, Thomas P, Kain AK, Parshad R.

PIP: The purpose of this study was to determine whether the antifertility effect
of the antiestrogenic substance neem oil, extracted from the seeds of
Azadirachta indica, acts directly on the uterus or through absorption from the
vaginal epithelium into the general circulation. In 4 groups of rats the left
uterine horn was ligated 2 days after coitus. Rats in group A were used as
controls. In group B 25 mcl neem oil was administered intravaginally on days
2-4 with the animals in head down position for 3 minutes to ensure that the neem
oil was uniformly distributed in the vagina. In group C the neem oil was
administered on days 4-6, and in group D on days 7-9, i.e., after implantation.
The ligatures were removed on day 12, and no viable implantation sites were
found in either horn. The study showed that the neem oil exerts its effect on
the endometrium through absorption into the general circulation from the vaginal
epithelium. The antiestrogenic quality of neem oil explains its
anti-implantation effect. But the postimplantation effect, which caused
implanted fetuses to be either resorbed or expelled, may be due to direct
toxicity, to a fall in progesterone level, or to interference with the uterine
utilization of progesterone.

PMID: 3225018 [PubMed - indexed for MEDLINE]

319: J Ethnopharmacol. 1988 May-Jun;23(1):53-9.

Non-hormonal post-coital contraceptive action of neem oil in rats.

Prakash AO, Tewari RK, Mathur R.

School of Studies in Zoology, Jiwaji University, Gwalior, India.

Neem oil, a natural product of Azadirachta indica was investigated for various
hormonal properties in relation to its post-coital contraceptive action. At
subcutaneous doses up to 0.3 ml/rat, neem oil did not possess any estrogenic,
anti-estrogenic or progestational activity and appeared not to interfere with
the action of progesterone. These findings were confirmed using the
histo-architecture of the uterus of treated rats. Since the post-coital
contraceptive effect of neem oil seems to be non-hormonal, neem oil would be
expected to elicit less side effects than the steroidal contraceptives.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 3419204 [PubMed - indexed for MEDLINE]

320: J Ethnopharmacol. 1988 May-Jun;23(1):39-51.

Acute toxicity study of the oil from Azadirachta indica seed (neem oil).

Gandhi M, Lal R, Sankaranarayanan A, Banerjee CK, Sharma PL.

Department of Pharmacology, Postgraduate Institute of Medical Education and
Research, Chandigarh, India.

The seed oil of Azadirachta indica (neem oil) is well known for its medicinal
properties in the indigenous Indian system of medicine. Its acute toxicity was
documented in rats and rabbits by the oral route. Dose-related pharmacotoxic
symptoms were noted along with a number of biochemical and histopathological
indices of toxicity. The 24-h LD50 was established as 14 ml/kg in rats and 24
ml/kg in rabbits. Prior to death, animals of both species exhibited comparable
pharmacotoxic symptoms in order and severity, with lungs and central nervous
system as the target organs of toxicity. Edible mustard seed oil (80 ml/kg) was
tested in the same manner to document the degree to which the physical
characteristics of an oil could contribute to the oral toxicity of neem oil.

PMID: 3419203 [PubMed - indexed for MEDLINE]

321: Int J Clin Pharmacol Ther Toxicol. 1988 Apr;26(4):176-84.

Folklore therapeutic indigenous plants in periodontal disorders in India
(review, experimental and clinical approach).

Patel VK, Venkatakrishna-Bhatt H.

Department of Pharmacology and Therapeutics, Government Dental College and
Hospitals, Asarva, Civil Hospital Compound, Ahmedabad, Gujarat, India.

Though a number of plants and their parts are used for dental ailments among
population in rural and urban areas of developing countries, in India however,
the most common house-hold, road-side plants are mango (Mangifera indica), neem
(Azadirachta indica; Melia azadirachta), ocimum (Ocimum basilicum), tea-dust
(Camellia sinensis) and uncommonly murayya, i.e., currey leaf (Murayya koenigi)
[Chopra et al. 1958, Kirtikar and Basu 1935, Nadakarni 1954, Satyavati 1984].
The leaves of these plants are folded and brushed (massage with teadust) against
the teeth. Therefore, the present study is restricted only to the fleshy leaf
extracts [Jindal et al. 1975] (except tea) of these plants inspite of certain
limitations in the methodology and arbitrations in the microbial identification
and isolation in the light of recent advances in folk dentistry. The
investigation was carried out in two parts: 1) Experimental study: The efficacy
of various dentifrices (commonly available in the market) and the potentiating
effect of the leaf extract (LE) of the aforesaid indigenous plants when
amalgamated with the tooth-paste against pathogens, were investigated. Further,
the protection afforded by the said plant extracts (PE) over the conventional
allopathic medicines on the human plaque cultures and gram negative bacteria
from patients were studied. 2) Clinical study: The therapeutic effects of the
said PE (individually) on clinical application among severely infected patients
were examined.

Publication Types:

PMID: 3042642 [PubMed - indexed for MEDLINE]

322: Indian J Malariol. 1987 Dec;24(2):111-7.

In vitro antimalarial activity of neem (Azadirachta indica A. Juss) leaf and
seed extracts.

Badam L, Deolankar RP, Kulkarni MM, Nagsampgi BA, Wagh UV.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 3330711 [PubMed - indexed for MEDLINE]

323: J Ethnopharmacol. 1987 Mar-Apr;19(2):125-31.

Immunomodulatory activity of an aqueous extract of Azadirachta indica stem bark.

van der Nat JM, Klerx JP, van Dijk H, de Silva KT, Labadie RP.

The interference of an aqueous extract of the stem bark of Azadirachta indica
with different parts of the human immune system was investigated. The extract
showed strong anticomplementary effects which were dose-and time-dependent and
most pronounced in the classical complement pathway assay. Moreover, a
dose-dependent decrease in the chemiluminescence of polymorphonuclear leukocytes
was observed and a dose-dependent increase in the production of migration
inhibition factor by lymphocytes.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 3302545 [PubMed - indexed for MEDLINE]

324: Vet Hum Toxicol. 1987 Feb;29(1):16-9.

The toxicity of Azadirachta indica leaves in goats and guinea pigs.

Ali BH.

The effects produced by the administration of aqueous suspensions of the green
or dried leaves of Azadirachta indica, a common tropical plant, were
investigated in goats and guinea pigs. At doses of 50 or 200 mg/kg given orally
over a period of up to eight weeks, the plant produced a progressive decrease in
body weight, weakness, inappetence, and loss of condition. There were also
decreases in heart, pulse and respiratory rates. Diarrhea was observed in
animals given the fresh leaves. In goats, the higher doses of the plant leaves
produced tremors and ataxia during the last few days of treatment. No
statistically significant hematological changes were observed after dosing the
animals with A indica leaves, although there was a tendency towards lowered
erythrocyte counts, packed cell volume and hemoglobin concentration. The
treatments caused significant rises in the plasma activity of aspartate
transferase, sorbitol dehydrogenase, and concentrations of cholesterol, urea,
creatinine and potassium. No significant changes in the plasma concentration of
sodium, chloride or bilirubin were detected. On necropsy of treated goats there
were areas of hemorrhagic erosions. The hearts appeared flappy and in some
animals there were hydropericarium. Histopathologically, there was evidence of
various degrees of hemorrhage, congestion, and degeneration in the liver,
kidney, lung, duodenum and brain. Degeneration of the seminiferous tubules was

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 3824869 [PubMed - indexed for MEDLINE]

325: J Ethnopharmacol. 1986 Jul;17(1):85-93.

Screening Azadirachta indica and Pisum sativum for possible antimalarial

Abatan MO, Makinde MJ.

Solvent-free extracts obtained from the leaves of Azadirachta indica and Pisum
sativum were screened for antimalarial action using Plasmodium berghei in mice.
Four days of oral dosing with 500 mg/kg and 125 mg/kg of the methanol extract of
A. indica showed a parasite suppression which was statistically significant
although all test animals died after 5 days, just 1 day longer than the
untreated control group. A 50 mg/kg oral dose of the aqueous extract of P.
sativum was found to have significant prophylactic activity by producing a
parasite suppression of 31.9%.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 3531729 [PubMed - indexed for MEDLINE]

326: Pharmacol Res Commun. 1986 Jan;18(1):81-91.

Biochemical mechanism of the antimalarial activity of Azadirachta indica leaf

Iwu MM, Obidoa O, Anazodo M.

The antimalarial herb, Azadirachta indica, acts by redox perturbation in the
form of the imposition of substantial oxidant stress during malarial infection.
The aqueous leaf extract substantially inhibited NADPH cytochrome C(P-450)
reductase activity in rats with a significant increase in the microsomal
protein. The aniline hydroxylase activity and the phenobarbitone metabolism were
also enhanced. The flavonoids quercetin-3-rhamnoside and quercetin-3-rutinoside
(rutin) were isolated as the major constituents of the extract. The significance
of these findings in clinical malaria chemotherapy is discussed.

PMID: 3081917 [PubMed - indexed for MEDLINE]

327: Southeast Asian J Trop Med Public Health. 1985 Mar;16(1):66-72.

Nimbolide, a constituent of Azadirachta indica, inhibits Plasmodium falciparum
in culture.

Rochanakij S, Thebtaranonth Y, Yenjai C, Yuthavong Y.

The terpenoid lactone nimbolide, the structure of which has been unambiguously
established, was found to inhibit Plasmodium falciparum in culture with a
moderate potency. The EC50 against the parasite line K1 from Thailand was
approximately 2.0 microM (0.95 microgram/ml). The EC50 of crude aqueous extract
of Azadirachta indica var. siamensis (Sadao tree), was 115 micrograms/ml, and of
crude ethanol extract was 5.0 micrograms/ml. Since nimbolide is a major
constituent in these extracts, it could account substantially for their
inhibitory activity. However, neither the crude extracts nor nimbolide showed
any activity in vivo against Plasmodium berghei in the mouse either through
ingestion (746 mg aqueous extract, 62.5 mg ethanol extract or 12.5 mg
nimbolide/kg/day), or subcutaneous injection (93 mg aqueous extract, 31 mg
ethanol extract or 12.5 mg nimbolide/kg/day).

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 3895455 [PubMed - indexed for MEDLINE]

328: Afr J Med Med Sci. 1985 Mar-Jun;14(1-2):51-4.

Effect of Azadirachta indica on Plasmodium berghei berghei in mice.

Obih PO, Makinde JM.

Azadirachta indica leaf extract has been investigated for antimalarial activity
against drug sensitive strain of P. berghei berghei in mice. On administering
the extract subcutaneously to infected mice in the "4-day schizontocidal test'
41.2% suppression of parasitaemia was observed. A similar observation was made
when the extract was injected for 3 days before the animals were infected with
the parasites, 21.7% chemosuppression was obtained. When treatment commenced
after the infection had already established, there was no demonstrable
suppression of parasitaemia.

PMID: 2994439 [PubMed - indexed for MEDLINE]

329: J Toxicol Environ Health. 1984;13(4-6):521-30.

The mutagenicities of seven coumarin derivatives and a furan derivative
(nimbolide) isolated from three medicinal plants.

Uwaifo AO.

Seven coumarin derivatives (imperatorin, heraclenin, xanthotoxin, marmesin,
chelepin, oxypeucedanin, esculin) and a furan derivative (nimbolide) were
screened on 6 Ames tester strains (TA92, TA94, TA97, TA98, TA100, TA102). The
eight compounds are chemicals isolated from three Nigerian medicinal plants:
Afraegle paniculata, Clausena anisata, and Azadirachta indica. Different
preparations of the former are taken by Nigerians for gut disturbances, and a
concoction of the latter called "Agbo" is taken as an antimalarial. Marmesin and
imperatorin were mutagenic in all tester strains except TA94 and TA102. The
mutagenicity potencies of marmesin and imperatorin were 20 and 0.2 respectively.
Mutagenicity was highest in TA98 and TA100 in both compounds. Marmesin was
optimally mutagenic at a dose of 1.04 micrograms, and imperatorin at 30.0
micrograms. Microsomal activation was not required for mutagenicity in both

PMID: 6387161 [PubMed - indexed for MEDLINE]

330: Environ Mutagen. 1983;5(5):687-94.

Mutagenicity testing of two tropical plant materials with pesticidal potential
in Salmonella typhimurium: Phytolacca dodecandra berries and oil from seeds of
Azadirachta indica.

Jongen WM, Koeman JH.

In this study the mutagenic potential of two tropical plant materials was
investigated in Salmonella typhimurium strains TA98 and TA100. The oil extract
from seeds of Azadirachta indica showed no mutagenic activity in either strain
with or without addition of metabolizing systems. When extracts of Phytolacca
dodecandra berries were tested, only the butanol extract caused direct
mutagenicity in TA98. After addition of rat liver homogenate, again only the
butanol extract was positive in TA98. Addition of gut flora extract as
metabolizing system generated positive effects in both the methanol extract and
the butanol extract. The water extract showed only a slight positive effect,
which can most probably be ascribed to the presence of histidine in the sample.

PMID: 6352253 [PubMed - indexed for MEDLINE]

331: Res Front Fertil Regul. 1982 Jun;2(1):1-16.

Current status of plant products reported to inhibit sperm.

Farnsworth NR, Waller DP.

PIP: This report reviews research on plant-derived agents that prevent sperm
production if taken orally by the male or that incapacitate or kill sperm on
contact if used vaginally by the female. It would be of great value to develop
fertility inhibitors that are totally selective for reproductive systems and
enzymes, and there is a possibility that a plant-derived drug may have this
effect. Plants that have been studied for their fertility inhibiting effects in
the male include: Aristolochia indica L. (Aristolochiaceae); Azadirachta indica
A. Juss (Meliaceae); Balanites roxburghii Planch. (Zygophyllaceae); Calotropis
procera (Ait) R.Br. (Asclepiadaceae); Carica papaya L. (Caricaceae);
Catharanthus roseus (L.) G. Don (Apocynaceae); Dieffenbachia seguine (Jacquin)
Schott. (Araceae); Ecaballium elaterium A. Richard (Cucurbitaceae); Gossypium
species (Malvaceae); Hibiscus rosa-sinensis L. (Malvaceae); Hippophae
salicifolia D. Don (Elaeagnaceae); Leucaena glauca (L.) Benth. (Leguminosae);
Lonicera ciliosa Poir. (Caprifoliaceae); Lupinus termis Forsk. (Leguminosae);
Malvaviscus conzattii Greenm. (Malvaceae); Momordica charantia L.
(Curcurbitaceae); Ocimum sanctum L. (Labiatae); Prunus emarginata Walp.
(Rosaceae); and Withania somnifera (L.) Dunal (Solanaceae). A large number of
plants have been randomly selected and screened for spermicidal activity "in
vitro" and several seem promising. Those species found to be active and the
nature of the active principle(s), when known, are presented in a table as are
plant-derived chemical substances of known or partially known structure reported
to be spermicidal "in vitro." Plants warrant systematic study as potential
sources of sperm-agglutinating compounds. Of 1600 Indian plants tested, 90
showed positive semen coagulating properties. There seems to be a lack of
correlation among experimental results obtained by different groups of
investigators, between data obtained "in vitro" and "in vivo," and between
experimental results and information found in folklore. Factors complicating
the adequate assessment of plants affecting male fertility are inadequate
numbers of vehicle-treated controls, poor experimental design, problems related
to insolubility of crude plant extracts, variation in routes of administration,
diversity in reproductive function and control among various laboratory species,
and problems in identifying plant names consistently.

PMID: 12179631 [PubMed - indexed for MEDLINE]

332: Indian J Biochem Biophys. 1981 Jun;18(3):202-5.

Studies on plant gums: Part VIII--Isolation & characterization of a high
molecular weight glycoprotein from neem (Azadirachta indica) gum.

Ramakrishna Nayak B, Pattabiraman TN.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 7309097 [PubMed - indexed for MEDLINE]

333: Planta Med. 1981 Jan;41(1):34-9.

Anti-inflammatory and antipyretic activities of Azadirachta indica.

Okpanyi SN, Ezeukwu GC.

PMID: 6972048 [PubMed - indexed for MEDLINE]

334: J Postgrad Med. 1980 Jul;26(3):167-70.

Male antifertility activity of Azadirachta Indica in mice.

Deshpande VY, Mendulkar KN, Sadre NL.

PMID: 7205685 [PubMed - indexed for MEDLINE]

335: Indian J Biochem Biophys. 1978 Dec;15(6):449-55.

Studies on plant gums: Part III--Isolation & characterization of a glycopeptide
from neem (Azadirachta indica) gum after pronase digestion.

Nayak BR, Pattabiraman TN.

PMID: 753744 [PubMed - indexed for MEDLINE]

336: J Pharm Sci. 1978 Oct;67(10):1476-8.

Cardiovascular effects of Azadirachta indica extract.

Thompson EB, Anderson CC.

A crude extract of the leaves of Azadirachta indica was studied for its effects
on the cardiovascular system of anesthetized guinea pigs and rabbits. These
effects include profound hypotension and a minimal negative chronotropic effect,
which increased at higher doses. In one rabbit, 200 mg of extract/kg decreased
the heart rate from 280 to 150 beats/min. The extract also exhibited a weak
antiarrhythmic activity in rabbits against ouabain-induced dysrhythmia.

PMID: 702308 [PubMed - indexed for MEDLINE]

337: J Pharm Pharmacol. 1974 Dec;26 Suppl:110P-111P.

Proceedings: Pharmacological studies on the leaves of Azadirachta indica.

Luscombe DK, Taha SA.

PMID: 4156703 [PubMed - indexed for MEDLINE]

338: Acta Microbiol Pol B. 1974;6(1):9-13.

Chemical compounds from Azadirachta indica as inhibitors of potato virus X.

Verma VS.

PMID: 4829363 [PubMed - indexed for MEDLINE]

339: Indian J Biochem Biophys. 1973 Sep;10(3):155-9.

Studies on plant gums. II. Separation of protein-rich and carbohydrate-rich
components of neem (Azadirachta indica) gum.

Narayan VS, Pattabiraman TN.

PMID: 4792919 [PubMed - indexed for MEDLINE]

340: Carbohydr Res. 1971 Dec;20(2):259-68.

The proteinaceous, gum polysaccharide from Azadirachta indica A. Juss.

Anderson DM, Hendrie A.

PMID: 5152099 [PubMed - indexed for MEDLINE]

341: Indian J Biochem. 1967 Sep;4(3):181-3.

Studies on plant gums: I--Identification of nitrogenous compounds in neem
(Azadirachta indica) gum and isolation of D-glucosamine.

Lakshmi SU, Pattabiraman TN.

Publication Types:
Comparative Study

PMID: 4233809 [PubMed - indexed for MEDLINE]

342: Curr Sci. 1951 May;20(5):127-8.

Structure of the neem (Azadirachta indica) gum.


PMID: 14849163 [PubMed - OLDMEDLINE]