Clinical Studies

Abstracts are presented below for clinical studies on Andrographis.

  • Botanical Name: Andrographis Paniculata

  • Ayurvedic Name: Bhunimba

  • Common Name: Andrographis

Andrographis Paniculata

Plant Phytonutrient Profile


1: Int Immunopharmacol. 2007 Apr;7(4):515-23. Epub 2007 Jan 17.

Modulation of immune response in mice immunised with an inactivated Salmonella
vaccine and gavaged with Andrographis paniculata extract or andrographolide.

Xu Y, Chen A, Fry S, Barrow RA, Marshall RL, Mukkur TK.

Department of Biological and Physical Sciences, Faculty of Sciences, University
of Southern Queensland, Toowoomba, Queensland 4350, Australia.

Gavage of mice, immunised with an inactivated S. typhimurium vaccine, with
Andrographis paniculata extract [APE] or andrographolide [AND] resulted in an
enhancement of Salmonella-specific antibody response and induction of
cell-mediated response against salmonellosis. Mice were vaccinated with either
one or two doses of killed S. typhimurium vaccine and fed two different
quantities of APE or AND, for 14 days in mice immunised with one dose of the
vaccine, and for 28 days in mice immunised with two doses of vaccine,
respectively. Both APE and AND were found to enhance IgG antibody levels against
S. typhimurium, the enhancement being statistically significant in mice
receiving two doses of the vaccine. Splenocyte cultures, prepared from mice
immunised with the killed Salmonella vaccine and treated with APE or AND, showed
a remarkable increase in the production IFN-gamma following stimulation with the
bacterial lysate, indicating an induction of Salmonella-specific cell-mediated
response/immune response.

PMID: 17321475 [PubMed - in process]

2: Asian Pac J Cancer Prev. 2006 Oct-Dec;7(4):609-14.

Ameliorating effects of Andrographis paniculata extract against
cyclophosphamide-induced toxicity in mice.

Sheeja K, Kuttan G.

Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur,
Kerala, India.

Major drawbacks of chemotherapeutic agents are their toxic side effects and lack
of tumor specificity. Immunological and biochemical studies were here carried
out to investigate protective effects of ethanolic extract of Andrographis
paniculata against cyclophosphamide (CTX) induced toxicity in vivo.
Intraperitoneal administration of the extract significantly increased the total
WBC account (3256.5+/-196 cells/cm(2)), bone marrow cellularity
(17.1+/-10.4x10(6) cells/femur) and betaesterase positive cells (849+/-23.2
cells/4000 cells) in CTX treated animals, when compared to CTX alone treated
control mice. Weights of lymphoid organs such as a spleen and thymus, reduced by
CTX administration, were also increased by A paniculata treatment. Reduction of
GSH in liver (4.8+/-0.21nmol/mg protein) and in intestinal mucosa (13+/-0.67
nmol/mg protein) of CTX-treated controls was significantly reversed by A
paniculata administration (liver: 6.4+/-0.13, intestinal mucosa: 17.11+/-0.06),
with amelioration of changes in serum and liver ALP, GPT, LPO (lipid
peroxidation). Histopathological analysis of small intestine also suggests that
extract could reduce the CTX induced intestinal damage. The level of
proinflammatory cytokine TNF-alpha, which was elevated during CTX
administration, was significantly reduced by the A paniculata extract
administration. The lowered levels of other cytokines like IFN-gamma, IL-2,
GM-CSF, after CTX treatment were also found to be increased by extract
administration.

PMID: 17250437 [PubMed - in process]

3: Phytochemistry. 2007 Jan 17; [Epub ahead of print]

Semisynthesis and in vitro anticancer activities of andrographolide analogues.

Jada SR, Subur GS, Matthews C, Hamzah AS, Lajis NH, Saad MS, Stevens MF,
Stanslas J.

Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400
Serdang, Selangor, Malaysia.

The plant Andrographis paniculata found throughout Southeast Asia contains
Andrographolide 1, a diterpenoid lactone, which has antitumour activities
against in vitro and in vivo breast cancer models. In the present study, we
report on the synthesis of andrographolide derivatives,
3,19-isopropylideneandrographolide (2),
14-acetyl-3,19-isopropylideneandrographolide (3) and 14-acetylandrographolide
(4), and their in vitro antitumour activities against a 2-cell line panel
consisting of MCF-7 (breast cancer cell line) and HCT-116 (colon cancer cell
line). Compounds 2 and 4 were also screened at the US National Cancer Institute
(NCI) for their activities against a panel of 60 human cancer cell lines derived
from nine cancer types. Compound 2 was found to be selective towards leukaemia
and colon cancer cells, and compound 4 was selective towards leukaemia, ovarian
and renal cancer cells at all the dose-response parameters. Compounds 2 and 4
showed non-specific phase of the cell cycle arrest in MCF-7 cells treated at
different intervals with different concentrations. NCI's COMPARE and SOM
mechanistic analyses indicated that the anticancer activities of these new class
of compounds were not similar to that of standard anticancer agents, suggesting
novel mechanism(s) of action.

PMID: 17234223 [PubMed - as supplied by publisher]

4: Int Immunopharmacol. 2007 Feb;7(2):211-21. Epub 2006 Nov 2.

Antiangiogenic activity of Andrographis paniculata extract and andrographolide.

Sheeja K, Guruvayoorappan C, Kuttan G.

Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur,
Kerala, India.

Inhibition of angiogenesis is currently perceived as one of the promising
strategies in the treatment of cancer. In this study we analyzed the
antiangiogenic activity of Andrographis paniculata extract (APE) and its major
component andrographolide (ANDLE) using both in vitro and in vivo models.
Intraperitoneal administration of APE and ANDLE significantly inhibited the
B16F-10 melanoma cell line induced capillary formation in C57BL/6 mice. Analysis
of serum cytokine profile showed a drastic elevation in the proinflammatory
cytokines such as IL-1beta, IL-6, TNF-alpha and GM-CSF and the most potent
angiogenic factor VEGF in angiogenesis induced animals. Treatment of APE and
ANDLE significantly reduced this elevated levels. Moreover, VEGF mRNA level in
B16F-10 cell line showed a reduced level of expression in the presence of APE
and ANDLE. Serum NO level which was increased in B16F-10 melanoma injected
control animals was also found to be significantly lowered by the administration
of APE and ANDLE. Antiangiogenic factors such as TIMP-1 and IL-2 level was
elevated in APE and ANDLE treated angiogenesis induced animals. In the rat
aortic ring assay APE and ANDLE inhibited the microvessel outgrowth at non toxic
concentrations. Taken together our results demonstrate that APE and ANDLE
inhibit the tumor specific angiogenesis by regulating the production of various
pro and antiangiogenic factors such as proinflammatory cytokine, nitric oxide,
VEGF, IL-2 and TIMP-1.

PMID: 17178389 [PubMed - in process]

5: Zhongguo Zhong Yao Za Zhi. 2006 Oct;31(19):1594-7.

[Studies on diterpenoids from Andrographis paniculata]

[Article in Chinese]

Chen LX, Qu GX, Qiu F.

Department of Natural Products Chemistry, Shenyang Pharmaceutical University,
Shenyang 110016, China.

OBJECTIVE: To study the diterpenoids in the 85% ethanol extract of the aerial
parts of Andrographis paniculata. METHOD: Fourteen diterpenoids from the 85%
EtOH extract were isolated by the silica gel, Sephadex LH-20, ODS column
chromatography and HPLC, and their structures were identified by the spectal
analyses and chemical evidences. RESULT: The 14 compounds were obtained and
identified as neoandrographolide (1), 3, 14-di-deoxyandrographolide (2),
andrographolide (3), 14-deoxy-11, 12-didehydroandrographolide (4), 19-hydroxy-8
(17), 13-labdadien-15, 16-olide (5), 14-deoxy-andrographolide (6),
3-oxo-14-deoxy-andrographolide (7), isoandrographolide, (8), bisandrographolide
(9, 10, 11), deoxyandrographiside (12), 14-deoxy-11, 12-didehydroandrographiside
(13), andrographiside (14), respectively. CONCLUSION: Compound 7 was a new
natural product, and compound 5 was obtained for the first time from the
Andrographis species.

Publication Types:
English Abstract

PMID: 17165582 [PubMed - in process]

6: J Chromatogr A. 2007 Jan 26;1140(1-2):71-7. Epub 2006 Dec 6.

On-line coupling of dynamic microwave-assisted extraction with high-performance
liquid chromatography for determination of andrographolide and
dehydroandrographolide in Andrographis paniculata Nees.

Chen L, Jin H, Ding L, Zhang H, Wang X, Wang Z, Li J, Qu C, Wang Y, Zhang H.

College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012,
China.

A novel technique based on dynamic microwave-assisted extraction (DMAE) coupled
on-line with high-performance liquid chromatography (HPLC) through a flow
injection interface has been developed for determination of andrographolide and
dehydroandrographolide in Andrographis paniculata Nees. A TM(010) microwave
resonance cavity built in the laboratory was applied to concentrating the
microwave energy. An extraction vessel was placed in microwave irradiation zone.
The extraction was performed in a recirculating system. When a number of
extraction cycles were completed, the fractional extract (20muL) was driven to
the analytical column by 65% aqueous methanol and was measured by diode array
detector (DAD) at 225nm. The optimized extraction conditions are follows:
extraction solvent 60% aqueous methanol; microwave forward power 80W; extraction
time 6min; extraction solvent flow-rate 1.0mLmin(-1). The detection and
quantification limits obtained are 0.5 and 1.7microgmL(-1) for andrographolide
and 0.6 and 1.9microgmL(-1) for dehydroandrographolide, respectively. The
within-day and between-day precision (RSD) are 2.1% and 3.7% for andrographolide
and 1.7% and 4.1% for dehydroandrographolide, respectively. Mean recoveries for
andrographolide and dehydroandrographolide are 97.7% and 98.7%, respectively.
Compared with ultrasonic extraction used in the Chinese pharmacopoeia, the
proposed method was demonstrated to obtain higher extraction yield in a shorter
time. In addition, only small quantities of solvent (5mL) and sample (10mg) were
required.

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

PMID: 17156791 [PubMed - in process]

7: J Ethnopharmacol. 2006 Oct 28; [Epub ahead of print]

Protective activity of andrographolide and arabinogalactan proteins from
Andrographis paniculata Nees. against ethanol-induced toxicity in mice.

Singha PK, Roy S, Dey S.

Microbiology and Immunology Laboratory, Department of Human Physiology with
Community Health, Vidyasagar University, Midnapore 721 102, West Bengal, India;
Plant Biotechnology Laboratory, Department of Biotechnology, IIT, Kharagpur 721
302, West Bengal, India.

To find out the active principles against ethanol-induced toxicity in mice,
Andrographis paniculata Nees. (Ap) was chosen and isolated andrographolide
(ANDRO) and arabinogalactan proteins (AGPs). ANDRO was detected by HPTLC, FTIR
and quantified by HPLC (10mg/g of Ap powder). AGPs was detected by beta-glucosyl
Yariv staining of SDS-PAGE gel, FTIR and quantified by single radial gel
diffusion assay with beta-glucosyl Yariv reagent (0.5mg/g Ap powder). The mice
are pretreated intra-peritoneally (i.p.) with different doses (62.5, 125, 250,
and 500mg/kg) of body weight of mice] of ANDRO and AGPs for 7 days and then
ethanol (7.5g/kg of body weight) was injected, i.p. Besides, silymarin was used
as standard hepatoprotective agent for comparative study with ANDRO and AGPs.
The ameliorative activity of ANDRO and AGP against hepatic renal alcohol
toxicity was measured by assessing GOT, GPT, ACP, ALP and LP levels in liver and
kidney. It has been observed that pretreatment of mice with ANDRO and AGPs at
500mg/kg of body weight and 125mg/kg of body weight respectively could able to
minimize the toxicity in compare to ethanol treated group as revealed by the
different enzymatic assay in liver and kidney tissues and the results were
comparable with silymarin. Hence, out of several ill-defined compounds present
in Ap, ANDRO and AGPs are the potential bioactive compounds responsible for
protection against ethanol-induced toxicity.

PMID: 17127022 [PubMed - as supplied by publisher]

8: Mol Cell Biochem. 2006 Nov 16; [Epub ahead of print]

Inhibitory effects of neoandrographolide on nitric oxide and prostaglandin E(2)
production in LPS-stimulated murine macrophage.

Liu J, Wang ZT, Ji LL, Ge BX.

Key Laboratory of Standardization of Chinese Medicines of Ministry of Education,
Institute of Chinese Material Medica, Shanghai University of Traditional Chinese
Medicine, 1200 Cailun Road, Zhangjiang Hi-Tech Park, Shanghai, 201203, P. R.
China, wangzht@hotmail.com.

Activated macrophages express inducible isoforms of nitric oxide synthase (iNOS)
and cyclooxygenase-2 (COX-2), produce excessive amounts of nitric oxide (NO) and
prostaglandin E(2) (PGE(2)), which play key roles in the processes of
inflammation. Andrographis paniculata Nees is a traditional Chinese herb
commonly used for treatment of infection, inflammation, and diarrhea. However,
the mechanism of its therapeutic function is not well known. In the present
study, the effect of neoandrographolide, one of bioactive components in A.
paniculata, on iNOS-mediated NO production and COX-2-mediated PGE(2) in
bacterial lipopolysaccharide (LPS) stimulated-murine macrophages was
investigated. Neoandrographolide at concentrations (30-90 muM) significantly (p
< 0.05) inhibited the productions of NO and PGE(2) in LPS stimulated macrophages
without inducing cytotoxicity. The effect of neoandrographolide also has been
investigated on iNOS and COX-2 expression in activated macrophage by using
RT-PCR and immunoblotting. The inhibition of NO release by neoandrographolide
can be attributed to the block of iNOS mRNA transcription followed by inhibiting
protein expression. However, neoandrographolide inhibited COX-2 protein
expression only but without inhibiting COX-2 mRNA expression, which was involved
in the inhibitory activity against the PGE(2 )overproduction. This suggests that
the effect of neoandrographolide on iNOS expression may occur at the
transcriptional level and the inhibition of COX-2 expression occurs at the
translational level. Furthermore, we have found that the addition of
neoandrographolide inhibited the activation of p38 mitogen-activated protein
kinase (MAPKs) instead of JNK, ERK1/2, or NF-kappaB. These results indicated
that the anti-inflammatory properties of neoandrographolide might result from
the inhibition of iNOS and COX-2 expression through inhibiting p38 MAPKs
activation. Therefore, neoandrographolide isolated from A. paniculata could be
offered as a leading compound for anti-inflammation.

PMID: 17109078 [PubMed - as supplied by publisher]

9: Eur J Pharmacol. 2006 Dec 28;553(1-3):39-45. Epub 2006 Sep 30.

Inhibitory effect of Andrographis paniculata extract and its active diterpenoids
on platelet aggregation.

Thisoda P, Rangkadilok N, Pholphana N, Worasuttayangkurn L, Ruchirawat S,
Satayavivad J.

Toxicology Graduate Programme, Faculty of Science, Mahidol University, Rama VI
Road, Bangkok 10400, Thailand; Laboratory of Pharmacology, Chulabhorn Research
Institute, Vipavadee-Rangsit Highway, Laksi, Bangkok 10210, Thailand.

Andrographis paniculata has been widely used for the prevention and treatment of
common cold especially in Asia and Scandinavia. The three active diterpenoids
from this plant, including aqueous plant extracts, were investigated for the
inhibitory effect on platelet aggregation in vitro. The results indicated that
andrographolide (AP(1)) and 14-deoxy-11,12-didehydroandrographolide (AP(3))
significantly inhibited thrombin-induced platelet aggregation in a
concentration-(1-100 microM) and time-dependent manner while neoandrographolide
(AP(4)) had little or no activity. AP(3) exhibited higher antiplatelet activity
than AP(1) with IC(50) values ranging from 10 to 50 microM. The inhibitory
mechanism of AP(1) and AP(3) on platelet aggregation was also evaluated and the
results indicated that the inhibition of extracellular signal-regulated
kinase1/2 (ERK1/2) pathway may contribute to antiplatelet activity of these two
compounds. In addition, standardized aqueous extracts of A. paniculata
containing different amounts of AP(3) inhibited thrombin-induced aggregation to
different degrees. The extracts significantly decreased platelet aggregation in
a concentration-(10-100 microg/ml) and time-dependent manner. However, the
extract with high level of AP(3) (Extract B) (IC(50) values=50-75 microg/ml)
showed less inhibitory activity against thrombin than the extract with lower
level of AP(3) (Extract A) (IC(50) values=25-50 microg/ml). These results
indicate that the standardized A. paniculata extract may contain other
antiplatelet compounds rather than AP(1) and AP(3), which contribute to high
antiplatelet activity. Therefore, the consumption of A. paniculata products may
help to prevent or treat some cardiovascular disorders i.e. thrombosis; however,
it should be used with caution by patients with bleeding disorders.

Publication Types:
In Vitro

PMID: 17081514 [PubMed - indexed for MEDLINE]

10: J Food Prot. 2006 Oct;69(10):2336-41.

Medicinal plant extracts as anti-Escherichia coli O157:H7 agents and their
effects on bacterial cell aggregation.

Voravuthikunchai SP, Limsuwan S.

Department of Microbiology, Faculty of Science, Prince of Songkla University,
Hatyai, Songkla 90112, Thailand. supayang.v@psu.ac.th

Ethanolic extracts of eight Thai medicinal plants (representing five families)
that are used as traditional remedies for treating diarrhea were examined with a
salt aggregation test for their ability to modulate cell surface hydrophobicity
of enterohemorrhagic Escherichia coli strains, including E. coli O157:H7. Four
of these medicinal plants, Acacia catechu, Peltophorum pterocarpum, Punica
granatum, and Quercus infectoria, have high bacteriostatic and bactericidal
activities. The ethanolic extract of Q. infectoria was the most effective
against all strains of E. coli, with MICs of 0.12 to 0.98 mg/ml and MBCs of 0.98
to 3.91 mg/ml. The ethanolic extract of P. granatum had MICs of 0.49 to 1.95
mg/ml and MBCs of 1.95 to 3.91 mg/ml. Ethanolic extracts of Q. infectoria, P.
pterocarpum, and P. granatum were among the most effective extracts against the
two strains of E. coli O157:H7. The other four plants, Andrographis paniculata,
Pluchia indica, Tamarindus indica, and Walsura robusta, did not have high
bacteriostatic and bactericidal activities but were able to affect
hydrophobicity characteristics on their outermost surface. All plants except Q.
infectoria had some ability to increase cell surface hydrophobicity. There
appears to be no correlation between antibacterial activity and cell aggregative
properties.

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

PMID: 17066910 [PubMed - indexed for MEDLINE]

11: Planta Med. 2006 Aug;72(10):954-6. Epub 2006 Aug 10.

Stability of andrographolide in powdered Andrographis herb under accelerated
conditions.

Plubrukarn A, Pinsuwan S, Ingkatawornwong S, Supavita T.

Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical
Sciences, Prince of Songkla University, Songkhla, Thailand.

The stability of andrographolide in powdered Andrographis Herb--the aerial part
of Andrographis paniculata (Burm. f.) Nees (Acanthaceae)--was determined using a
heat-accelerated experiment to reveal a second-order kinetics of degradation.
The fast decomposition was observed regardless of the method of analysis. The
rate constant of the decomposition of andrographolide at 25 degrees C ( K(25)(
degrees C)), predicted from the Arrhenius plot, was 6.58 x 10 (-6) d (-1).

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

PMID: 16902869 [PubMed - indexed for MEDLINE]

12: J Biol Chem. 2006 Oct 6;281(40):29897-904. Epub 2006 Aug 9.

Bisandrographolide from Andrographis paniculata activates TRPV4 channels.

Smith PL, Maloney KN, Pothen RG, Clardy J, Clapham DE.

Department of Cardiology, Howard Hughes Medical Institute, Children's Hospital,
Boston, Massachusetts 02115, USA.

Many transient receptor potential (TRP) channels are activated or blocked by
various compounds found in plants; two prominent examples include the activation
of TRPV1 channels by capsaicin and the activation of TRPM8 channels by menthol.
We sought to identify additional plant compounds that are active on other types
of TRP channels. We screened a library of extracts from 50 Chinese herbal plants
using a calcium-imaging assay to find compounds active on TRPV3 and TRPV4
channels. An extract from the plant Andrographis paniculata potently activated
TRPV4 channels. The extract was fractionated further, and the active compound
was identified as bisandrographolide A (BAA). We used purified compound to
characterize the activity of BAA on certain TRPV channel subtypes. Although BAA
activated TRPV4 channels with an EC(50) of 790-950 nm, it did not activate or
block activation of TRPV1, TRPV2, or TRPV3 channels. BAA activated a large
TRPV4-like current in immortalized mouse keratinocytes (308 cells) that have
been shown to express TRPV4 protein endogenously. This compound also activated
TRPV4 currents in cell-free outside-out patches from HEK293T cells
overexpressing TRPV4 cDNA, suggesting that BAA can activate the channel in a
membrane-delimited manner. Another related compound, andrographolide, found in
abundance in the plant Andrographis was unable to activate or block activation
of TRPV4 channels. These experiments show that BAA activates TRPV4 channels, and
we discuss the possibility that activation of TRPV4 by BAA could play a role in
some of the effects of Andrographis extract described in traditional medicine.

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

PMID: 16899456 [PubMed - indexed for MEDLINE]

13: Trop Biomed. 2005 Dec;22(2):165-70.

In vitro screening of five local medicinal plants for antibacterial activity
using disc diffusion method.

Zaidan MR, Noor Rain A, Badrul AR, Adlin A, Norazah A, Zakiah I.

Bioassay Unit, Herbal Medicine Research Centre, Institute for Medical Research,
Kuala Lumpur.

Medicinal plants have many traditional claims including the treatment of
ailments of infectious origin. In the evaluation of traditional claims,
scientific research is important. The objective of the study was to determine
the presence of antibacterial activity in the crude extracts of some of the
commonly used medicinal plants in Malaysia, Andrographis paniculata, Vitex
negundo, Morinda citrifolia, Piper sarmentosum, and Centella asiatica. In this
preliminary investigation, the leaves were used and the crude extracts were
subjected to screening against five strains of bacteria species, Methicillin
Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Klebsiella
pneumoniae, Pseudomonas aeruginosa and Escherichia coli, using standard protocol
of Disc Diffusion Method (DDM). The antibacterial activities were assessed by
the presence or absence of inhibition zones and MIC values. M. citrifolia, P.
sarmentosum and C. asiatica methanol extract and A. paniculata (water extract)
have potential antibacterial activities to both gram positive S. aureus and
Methicillin Resistant S. aureus (MRSA). None of the five plant extracts tested
showed antibacterial activities to gram negative E. coli and K. pneumoniae,
except for A. paniculata and P. sarmentosum which showed activity towards P.
aeruginosa. A. paniculata being the most potent at MIC of 2 g/disc. This finding
forms a basis for further studies on screening of local medicinal plant extracts
for antibacteria properties.

PMID: 16883283 [PubMed - in process]

14: Integr Cancer Ther. 2006 Sep;5(3):244-51.

Protective effect of Andrographis paniculata and andrographolide on
cyclophosphamide-induced urothelial toxicity.

Sheeja K, Kuttan G.

Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India.

The protective effect of Andrograhis paniculata and andrographolide (ANDLE)
against cyclophosphamide (CTX)-induced urothelial toxicity was investigated in
this study. Pretreatment of Swiss albino mice with A paniculata extract (10
mg/dose/animal intraperitoneally [ip]) and ANDLE (500 microg/dose/animal ip)
could significantly reduce CTX (1.5 nmol/kg body weight)-induced urothelial
toxicity. Morphological and histopathological analysis of urinary bladder of
CTX-treated mice showed severe inflammation and dark coloration, whereas A
paniculata and ANDLE-treated mice showed almost normal bladder morphology.
Elevation of urinary protein level (7.33 +/- 0.3 g/L) by CTX administration was
reduced by A paniculata (3.78 +/- 0.4 g/L) and ANDLE treatment (4.19 +/- 0.1
g/L). Urinary urea N2 level, which was elevated after 48 hours of CTX
administration (24.25 +/- 0.2 g/L) was found to be reduced by the treatment with
A paniculata (14.19 +/- 0.5 g/L) and ANDLE (15.79 +/- 0.4 g/L). A decreased
level of reduced glutahione (GSH) content in liver (2.81 +/- 0.1 nmol/mg
protein) and bladder (1.20 +/- 0.2 nmol/mg protein) after CTX administration was
also increased by the treatment with A paniculata (liver: 5.78 +/- 0.3 nmol/mg
protein; bladder: 2.96 +/- 0.2 nmol/mg protein) and ANDLE (liver: 5.14 +/- 0.3
nmol/mg protein; bladder: 2.84 +/- 0.2 nmol/mg protein). Production of the
proinflammatory cytokine, tumor necrosis factor-alpha, which was elevated during
CTX administration, was found to be inhibited by A paniculata and ANDLE
treatment. The lowered level of interleukin-2 and interferon-gamma during CTX
treatment was elevated by the administration of A paniculata and ANDLE.

PMID: 16880430 [PubMed - indexed for MEDLINE]

15: J Enzyme Inhib Med Chem. 2006 Apr;21(2):145-55.

Erratum in:
J Enzyme Inhib Med Chem. 2006 Jun;21(3):327.

Semisynthesis and cytotoxic activities of andrographolide analogues.

Jada SR, Hamzah AS, Lajis NH, Saad MS, Stevens MF, Stanslas J.

Clinical Pharmacology Laboratory, Division of Medical Sciences, National Cancer
Centre, 11 Hospital Drive, 169610, Singapore.

Andrographolide 1, a diterpenoid lactone of the plant Andrographis paniculata,
known to possess antitumour activity in in vitro and in vivo breast cancer
models was subjected to semisynthesis leading to the preparation of a number of
novel compounds. These compounds exhibited in vitro antitumour activity with
moderate to excellent growth inhibition against MCF-7 (breast) and HCT-116
(colon) cancer cells. Compounds 3,19-(2-chlorobenzylidene)andrographolide(5),
3,19-(3-chlorobenzylidene)andrographolide(6), 3,19-(3-fluorobenzylidene)
andrographolide(7), 3,19-(4-fluorobenzylidene)andrographolide(8),
3,19-(2-fluorobenzylidene)andrographolide(10),
3,19-(2-chloro-5-nitrobenzylidene)andrographolide (21),
3,19-(4-chlorobenzylidene)andrographolide(30) and
3,19-(2-chloro-4-fluorobenzylidene) andrographolide(31) were also screened
against 60 NCI (National Cancer Institute, USA) human tumour cell lines derived
from nine cancer cell types.

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

PMID: 16789428 [PubMed - indexed for MEDLINE]

16: Explore (NY). 2006 Jan;2(1):25-9.

Andrographis paniculata for the treatment of upper respiratory infection: a
systematic review by the natural standard research collaboration.

Kligler B, Ulbricht C, Basch E, Kirkwood CD, Abrams TR, Miranda M, Singh Khalsa
KP, Giles M, Boon H, Woods J.

Continuum Center for Health and Healing, New York, NY, USA.
bkligler@bethisraelny.org

Publication Types:
Review

PMID: 16781605 [PubMed - indexed for MEDLINE]

17: Biochem Pharmacol. 2006 Jul 14;72(2):132-44. Epub 2006 Apr 29.

Critical role of pro-apoptotic Bcl-2 family members in andrographolide-induced
apoptosis in human cancer cells.

Zhou J, Zhang S, Ong CN, Shen HM.

Department of Community, Occupational and Family Medicine, Yong Loo Lin School
of Medicine, National University of Singapore, 16 Medical Drive, Singapore
117597, Republic of Singapore.

Andrographolide (Andro), a diterpenoid lactone isolated from a traditional
herbal medicine Andrographis paniculata, is known to possess potent
anti-inflammatory activity. In this study, Andro induced apoptosis in human
cancer cells via activation of caspase 8 in the extrinsic death receptor pathway
and subsequently with the participation of mitochondria. Andro triggered a
caspase 8-dependent Bid cleavage, followed by a series of sequential events
including Bax conformational change and mitochondrial translocation, cytochrome
c release from mitochondria, and activation of caspase 9 and 3. Inhibition of
caspase 8 blocked Bid cleavage and Bax conformational change. Consistently,
knockdown of Bid protein using small interfering RNA (siRNA) technique
suppressed Andro-induced Bax conformational change and apoptosis. In conclusion,
the pro-apoptotic Bcl-2 family members (Bid and Bax) are the key mediators in
relaying the cell death signaling initiated by Andro from caspase 8 to
mitochondria and then to downstream effector caspases, and eventually leading to
apoptotic cell death.

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

PMID: 16740251 [PubMed - indexed for MEDLINE]

18: Zhongguo Zhong Yao Za Zhi. 2006 Mar;31(5):391-5.

[Studies on flavonoids of Andrographis paniculata]

[Article in Chinese]

Chen LX, Qu GX, Qiu F.

Shenyang Pharmaceutical University, China.

OBJECTIVE: To study the flavonoids of the aerial parts of Andrographis
paniculata. METHOD: Twelve flavonoids from the 85% EtOH extract were isolated by
the silica gel column, Sephadex LH-20 column, ODS column chromatography and
HPLC, and their structures were identified by the spectal analyses and chemical
evidences. RESULT: The 12 compounds were obtained and identified as
7-O-methylwogonin (1), 7-O-methyldihydrowogonin (2), 5-hydroxy-7, 8, 2',
5'-tetramethoxy-flavone (3), skullcapflavone-2'-methoxylether (4), 5-hydroxy-7,
8, 2', 3'-tetramethoxyflavone (5), 5, 4'-dihydroxy-7, 8, 2',
3'-tetramethoxyflavone (6), dihydroskullcapflavone (7), 5, 7,
8-trimethoxydihydroflavone (8), 5, 2'-dihydroxy-7, 8-dimethoxyflvone (9),
andrographidine C (10), 5, 7, 4'-trihydroxyflavone (11), 5, 7, 3',
4'-tetrahydroxyflavone (12). CONCLUSION: Compound 6 is a new naturally occurring
product isolated from A. paniculata, and compound 8, 11 and 12 are obtained for
the first time from the Andrographis species.

Publication Types:
English Abstract

PMID: 16711423 [PubMed - indexed for MEDLINE]

19: Immunopharmacol Immunotoxicol. 2006;28(1):129-40.

Antioxidant and anti-inflammatory activities of the plant Andrographis
paniculata Nees.

Sheeja K, Shihab PK, Kuttan G.

Amala Cancer Research Centre, Thrissur, Kerala, India.

In this study, we explored the antioxidant and anti-inflammatory properties of
the medicinal herb Andrographis paniculata using in vitro as well as in vivo
systems. Methanolic extract of Andrographis paniculata was found to inhibit
formation of oxygen derived free radicals such as superoxide (32%) hydroxyl
radicals (80%) lipid peroxidation (80%) and nitric oxide (42.8%) in in vitro
system. In vivo studies using BALB/c mice models also showed significant
inhibition in PMA induced superoxide (32.4%) and nitric oxide (65.3%) formation.
Interestingly we also found that, administration of Andrographis paniculata
extract produced complete inhibition of carageenan induced inflammation compared
with control models.

PMID: 16684672 [PubMed - indexed for MEDLINE]

20: Phytomedicine. 2006 May;13(5):318-23. Epub 2005 Sep 16.

The effect of Kan Jang extract on the pharmacokinetics and pharmacodynamics of
warfarin in rats.

Hovhannisyan AS, Abrahamyan H, Gabrielyan ES, Panossian AG.

"Exlab" Expert Analytical Laboratory of Drug and Medical Technology Agency of
Ministry of Health, Yerevan, Armenia. arego@sci.am

Significant pharmacokinetic/pharmacodynamic interactions between various herbal
products and warfarin have recently been reported. The aim of this study was to
determine whether concomitant treatment of rats with Kan Jang (a standardized
fixed combination of extracts from Andrographis paniculata and Eleutherococcus
senticosus) and warfarin would lead to an alteration in the pharmacological
effects of warfarin. Each day for 5 days a group of animals was treated orally
with an aqueous solution of Kan Jang at a dose of 17 mg/kg of the active
principle andrographolide (a daily dose some 17-fold higher than that
recommended for humans): the control group received similar treatment with
appropriate volumes of water only. Sixty minutes after the final daily
administration of Kan Jang or water, an aqueous solution of warfarin (0.2 mg/ml)
was given to each animal at a dose of 2 mg/kg. From each group, 6 animals were
sacrificed at 0, 2, 4, 6, 8, 12, 24, 30 and 48 h after warfarin administration
and blood samples taken. The concentration of warfarin in blood plasma was
measured by capillary electrophoresis using 50 mM borate buffer (pH 9.3) as
mobile phase with simultaneous detection of warfarin at 208.1 and 307.5 nm.
Prothrombin time in blood plasma was measured using thromboplastin reagent. The
concomitant application of Kan Jang and warfarin did not produce significant
effects on the pharmacokinetics of warfarin, and practically no effect on its
pharmacodynamics.

Publication Types:
Comparative Study

PMID: 16635739 [PubMed - indexed for MEDLINE]

21: J Ethnopharmacol. 2006 Sep 19;107(2):205-10. Epub 2006 Mar 17.

The effect of medicinal plants used in Chinese folk medicine on RANTES secretion
by virus-infected human epithelial cells.

Ko HC, Wei BL, Chiou WF.

Division of Basic Chinese Medical Research, National Research Institute of
Chinese Medicine, Shipai, Taipei, Taiwan, ROC.

The accumulation of inflammatory cells in the infective sites has been reported
to play a crucial role in the progression of chronic inflammation and multiple
sclerosis after viral infection. In the present study, nine ethanol extracts of
Forsythia suspensa Vahl. (Oleaceae), Lonicera japonica Thunb. (Caprifoliaceae),
Isatis indigotica Fort. (Cruciferae), Strobilanthes cusia (Ness.) O. Kuntze
(Acanthaceae), Astragalus membranaceus (Fisch.) Bge. (Leguminosae), Hedysarum
polybotrys Hand.-Mazz. (Leguminosae), Andrographis paniculata (Burm. f.) Ness.
(Acanthaceae), Glycyrrhiza uralensis Fischer. (Leguminosae) and Ligusticum
wallichii Franch. (Umbelliferae), medicinal plants traditionally used in China
for treating conditions likely to be associated with inflammation and viral
infection, were screened for their effect on RANTES secretion by influenza A
virus (H1N1)-infected human bronchial epithelial cells (A549). With exception of
Lonicera japonica, Isatis indigotica, Astragalus membranaceus and Hedysarum
polybotrys, all plants tested at concentration of 200 microg/ml possessed more
than 50% suppressing effect on RANTES secretion by H1N1-infected A549 bronchial
epithelial cells. Among the plants tested, Andrographis paniculata showed the
most promising property to inhibit RANTES secretion with an IC(50) of 1.2 +/-
0.4 microg/ml while the next two were Glycyrrhiza uralensis and Forsythia
suspensa (IC(50) ranging from 35 to 48 microg/ml).

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

PMID: 16621378 [PubMed - indexed for MEDLINE]

22: J Nat Prod. 2006 Mar;69(3):403-5.

Andropanolide and isoandrographolide, minor diterpenoids from Andrographis
paniculata: structure and X-ray crystallographic analysis.

Pramanick S, Banerjee S, Achari B, Das B, Sen AK Sr, Mukhopadhyay S, Neuman A,
Prange T.

Indian Institute of Chemical Biology, Kolkata, India.

Phytochemical investigation of the leaves of Andrographis paniculata has led to
the isolation of a new labdane type diterpenoid, andropanolide (1), along with
seven known diterpenoids including isoandrographolide (2), previously reported
as a rearrangement product of andrographolide. The structures and
stereochemistry of compounds 1 and 2 were established by X-ray crystallographic
analysis.

PMID: 16562845 [PubMed - indexed for MEDLINE]

23: J Nat Prod. 2006 Mar;69(3):319-22.

ent-Labdane diterpenoids from Andrographis paniculata.

Shen YH, Li RT, Xiao WL, Xu G, Lin ZW, Zhao QS, Sun HD.

State Key Laboratory of Phytochemistry and Plant Resources in West China,
Kunming Institute of Botany, Chinese Academy of Sciences, People's Republic of
China.

Six new ent-labdane diterpenoids,
3-O-beta-D-glucopyranosyl-14,19-dideoxyandrographolide (1),
14-deoxy-17-hydroxyandrographolide (2),
19-O-[beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranoyl]-3,14-dideoxyandrographol
ide (3), 3-O-beta-d-glucopyranosylandrographolide (4),
12S-hydroxyandrographolide (5), and andrographatoside (6), together with 17
known analogues, were isolated from the aerial parts of Andrographis paniculata.
The structures of 1-6 were determined by spectroscopic data analysis. All
compounds isolated were evaluated for their inhibitory activity against several
bacterial and fungal strains.

PMID: 16562826 [PubMed - indexed for MEDLINE]

24: J Ethnopharmacol. 2006 May 24;105(3):464-7. Epub 2006 Jan 6.

Impact of Andrographis paniculata crude extract on mouse hepatic cytochrome P450
enzymes.

Jarukamjorn K, Don-in K, Makejaruskul C, Laha T, Daodee S, Pearaksa P,
Sripanidkulchai BO.

Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon
Kaen University, Khon Kaen 40002, Thailand. kanok_ja@kku.ac.th

Modulatory influence of Andrographis paniculata crude extract on cytochrome P450
(CYP) enzymes was performed by administration of the crude extract of
Andrographis paniculata to ICR male mice. Total hepatic P450 content was not
significantly modified by either the aqueous or the alcoholic extracts of
Andrographis paniculata. Assessment of hepatic microsomal P450 activities by
alkoxyresorufin O-dealkylations noted that both the aqueous and alcoholic
extracts of Andrographis paniculata significantly increased ethoxyresorufin
O-dealkylase and pentoxyresorufin O-dealkylase activities, while those of
methoxyresorufin O-dealkylase activities were not elevated. These results
suggested that Andrographis paniculata might effectuate hepatic cytochrome P450
enzymes of which CYP1A1 and CYP2B are the responsive P450 isoforms.

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

PMID: 16406417 [PubMed - indexed for MEDLINE]

25: Phytother Res. 2006 Jan;20(1):79-81.

Inhibitory effect of Thai plant extracts on P-glycoprotein mediated efflux.

Junyaprasert VB, Soonthornchareonnon N, Thongpraditchote S, Murakami T, Takano
M.

Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447
Sri-Ayutthaya, Rajathavee, Bangkok 10400, Thailand. pyvbp@mahidol.ac.th

Curcuminoids from Curcuma longa L. and extracts of Psidium guajava L.,
Andrographis paniculata (Burm. f.) Nees, Phyllanthus emblica L. and Solanum
trilobatum L. were investigated for their inhibitory effect on P-glycoprotein
(P-gp) on the efflux transport of rhodamine 123 (Rho-123 ) in Caco-2 cells and
rat ileum. Of the five tested samples, curcuminoids and an extract of P. guajava
showed the highest inhibitory effect on P-gp mediated efflux of Rho-123 in
Caco-2 cells. Additionally, they were found to have equal potential in
inhibiting Rho-123 efflux transport from serosal to mucosal surfaces of the rat
ileum. Copyright 2006 John Wiley & Sons, Ltd.

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

PMID: 16397849 [PubMed - indexed for MEDLINE]

26: Planta Med. 2005 Dec;71(12):1106-11.

Andrographolide isolated from Andrographis paniculata induces cell cycle arrest
and mitochondrial-mediated apoptosis in human leukemic HL-60 cells.

Cheung HY, Cheung SH, Li J, Cheung CS, Lai WP, Fong WF, Leung FM.

Department of Biology and Chemistry, City University of Hong Kong, Hong Kong
SAR, China. bhhonyun@cityu.edu.hk

The in vitro cytotoxicities of the ethanol extract of Andrographis paniculata
(APE) and its main diterpenoid components were evaluated in various cancer
cells. APE was found to be significantly growth inhibitory to human acute
myeloid leukemic HL-60 cells with an IC (50) value of 14.01 microg/mL after 24 h
of treatment. Among the three main diterpenoids in A. paniculata,
andrographolide exhibited the highest degree of cytotoxicity followed by
deoxyandrographolide while neoandrographolide was the least effective. Laser
confocal microscopy and gel electrophoresis studies revealed chromosomal DNA
fragmentations suggesting the occurrence of apoptosis. An increase of G (0)/G
(1) phase cells from 51.88 % to 78.69 % was noted after andrographolide
treatment for 36 h. The G (0)/G (1) phase arrest and apoptosis were associated
with disappearance of mitochondrial cytochrome c and increased expression of Bax
but decreased expression of Bcl-2 proteins in the inhibited cells. Although the
order of all these events has not been determined, it is concluded that APE and
andrographolide induce cell cycle arrest and affect an intrinsic
mitochondria-dependent pathway of apoptosis by regulating the expression of some
pro-apoptotic markers in HL-60 cells.

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

PMID: 16395645 [PubMed - indexed for MEDLINE]

27: Am J Health Syst Pharm. 2006 Jan 1;63(1):33-9.

Complementary and alternative medicine for upper-respiratory-tract infection in
children.

Carr RR, Nahata MC.

College of Pharmacy, The Ohio State University, Columbus, OH 43210-1291, USA.

PURPOSE: Evidence on the efficacy and safety of complementary and alternative
medicine (CAM) for the prevention and treatment of upper-respiratory-tract
infection (URTI) in children is reviewed. SUMMARY: A search of the literature to
June 2005 identified six clinical trials examining the use of herbal medicines
and nine trials of other CAM therapies. All articles were critically evaluated
for adherence to standards of efficacy and safety research. Echinacea did not
reduce the duration and severity of URTI. Andrographis paniculata or echinacea
decreased nasal secretions (p < 0.01) but not URTI symptoms. A combination of
echinacea, propolis, and ascorbic acid decreased the number of URTI episodes,
the duration of symptoms, and the number of days of illness (p < 0.001).
Echinacea was associated with a higher frequency of rash compared with placebo
(p = 0.008). Neither ascorbic acid nor homeopathy was effective. The efficacy of
zinc was not clear, and zinc may be associated with adverse effects in children.
Osteopathic manipulation decreased episodes of acute otitis media (p = 0.04) and
the need for tympanostomy tube insertion (p = 0.03) in children with recurrent
acute otitis media. Stress-management therapy reduced the duration of URTI
compared with relaxation therapy with guided imagery or standard care (p <
0.05). CONCLUSION: Current data are generally inadequate to support CAM for the
prevention or treatment of URTI in children.

Publication Types:
Review

PMID: 16373463 [PubMed - indexed for MEDLINE]

28: Phytother Res. 2005 Dec;19(12):1069-70.

Antiviral properties of ent-labdene diterpenes of Andrographis paniculata nees,
inhibitors of herpes simplex virus type 1.

Wiart C, Kumar K, Yusof MY, Hamimah H, Fauzi ZM, Sulaiman M.

Department of Pharmacy, Faculty of Medicine, University of Malaya, Malaysia.
christophe_wiart@yahoo.com

Andrographolide, neoandrographolide and 14-deoxy-11,12-didehydroandrographolide,
ent-labdene diterpenes isolated from Andrographis paniculata showed viricidal
activity against herpes simplex virus 1 (HSV-1). None of these compounds
exhibited significant cytotoxicity at viricidal concentrations. Copyright 2005
John Wiley & Sons, Ltd.

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

PMID: 16372376 [PubMed - indexed for MEDLINE]

29: Se Pu. 2002 Sep;20(5):446-8.

[Determination of andrographolide and dehydroandrographolide in Andrographis
paniculata nees materials and related patent medicines by reversed-phase high
performance liquid chromatography]

[Article in Chinese]

Xu XQ, Hu GL, Shen JC, Li Q, Wang XR.

The Key Laboratory of Analytical Sciences of Ministry of Education of China,
College of Chemistry and Chemical Engineering, Xiamen Unitersity, Xiamen 361005,
China.

A simple and accurate method for the determination of andrographolide and
dehydroandrographolide in andrographis paniculata Nees materials and patent
medicines with high performance liquid chromatography (HPLC) has been developed.
The two components were extracted from powdered samples by shaking with
methanol. The resultant extracts were separated within 15 min on a BECKMAN C18
column (4.6 mm i. d. x 250 mm, 5 microm) and with a gradient elution of
acetonitrile-water at a flow rate of 0.5 mL/min. The detection wavelength was
225 nm and the injection volume was 20 microL. In gradient elution program the
volume fraction of acetonitrile in mobile phase was as follows: 0 min - 1 min,
40%; 1 min - 5 min, 40% - 50%; 5 min - 15 min, 50% - 70%. Both andrographolide
and dehydroandrographolide have good linearity in the range of 10 mg/L to 100
mg/L with the correlation coefficients of 0.997 6 and 0.998 6 respectively. This
method has been successfully applied for the analysis of andrographis paniculata
Nees materials and related patent medicines.

Publication Types:
English Abstract

PMID: 16358699 [PubMed - in process]

30: J Ethnopharmacol. 2006 Apr 21;105(1-2):196-200. Epub 2005 Nov 18.

Anti-diabetic potentials of Momordica charantia and Andrographis paniculata and
their effects on estrous cyclicity of alloxan-induced diabetic rats.

Reyes BA, Bautista ND, Tanquilut NC, Anunciado RV, Leung AB, Sanchez GC, Magtoto
RL, Castronuevo P, Tsukamura H, Maeda KI.

Thomas Jefferson University, Department of Neurosurgery, Farber Institute for
Neurosciences, Philadelphia, Pennsylvania 19107, USA. bsr103@jefferson.edu

Momordica charantia and Andrographis paniculata are the commonly used herbs by
the diabetic patients in Pampanga, Philippines. While the anti-diabetic
potential of Momordica charantia is well established in streptozocin- or
alloxan-induced diabetic animals, the anti-diabetic potential of Andrographis
paniculata in alloxan-induced diabetic rat is not known. Neither the effects of
these herbs on estrous cyclicity of alloxan-induced diabetic rats are
elucidated. Thus, in these experiments, Momordica charantia fruit juice or
Andrographis paniculata decoction was orally administered to alloxan-induced
diabetic rats. Rats that were treated with Momordica charantia and Andrographis
paniculata had higher body weight (BW) compared with diabetic positive control
(P < 0.01) from day 22 to day 27 (D27) but exhibited lower BW than the
non-diabetic control (P < 0.05). These rats had lower feed (P < 0.05) and liquid
intakes (P < 0.01) compared with diabetic positive control from day 17 to D27,
but similar with the non-diabetic control. The blood glucose levels in these
groups were significantly reduced from day 12 to D27 compared with diabetic
positive control (P < 0.01), however, comparable with non-diabetic control. The
diabetic positive control had extended mean estrous cycles (8 days) compared to
Momordica charantia and Andrographis paniculata-treated diabetic rats (5 days; P
< 0.05). Our results suggest that the anti-diabetic potentials of Momordica
charantia and Andrographis paniculata could restore impaired estrous cycle in
alloxan-induced diabetic rats.

PMID: 16298503 [PubMed - indexed for MEDLINE]

31: J Ethnopharmacol. 2006 Jan 16;103(2):201-7. Epub 2005 Sep 15.

Screening of plants acting against Heterometrus laoticus scorpion venom activity
on fibroblast cell lysis.

Uawonggul N, Chaveerach A, Thammasirirak S, Arkaravichien T, Chuachan C, Daduang
S.

Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen
40002, Thailand.

The aqueous extracts of 64 plant species, listed as animal- or insect-bite
antidotes in old Thai drug recipes were screened for their activity against
fibroblast cell lysis after Heterometrus laoticus scorpion venom treatment. The
venom was preincubated with plant extract for 30 min and furthered treated to
confluent fibroblast cells for 30 min. More than 40% efficiency (test/control)
was obtained from cell treatment with venom preincubated with extracts of
Andrographis paniculata Nees (Acanthaceae), Barringtonia acutangula (L.) Gaertn.
(Lecythidaceae), Calamus sp. (Palmae), Clinacanthus nutans Lindau (Acanthaceae),
Euphorbia neriifolia L. (Euphorbiaceae), Ipomoea aquatica Forssk
(Convolvulaceae), Mesua ferrea L. (Guttiferae), Passiflora laurifolia L.
(Passifloraceae), Plectranthus amboinicus (Lour.) Spreng. (Labiatae), Ricinus
communis L. (Euphorbiaceae), Rumex sp. (Polygonaceae) and Sapindus rarak DC.
(Sapindaceae), indicating that they had a tendency to be scorpion venom
antidotes. However, only Andrographis paniculata and Barringtonia acutangula
extracts provided around 50% viable cells from extract treatments without venom
preincubation. These two plant extracts are expected to be scorpion venom
antidotes with low cytotoxicity.

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

PMID: 16169172 [PubMed - indexed for MEDLINE]

32: Planta Med. 2005 Jul;71(7):604-8.

14-deoxyandrographolide as a platelet activating factor antagonist in bovine
neutrophils.

Burgos RA, Hidalgo MA, Monsalve J, LaBranche TP, Eyre P, Hancke JL.

Laboratory of Molecular Pharmacology, Institute of Pharmacology, Facultad de
Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
rburgos1@uach.cl

14-Deoxyandrographolide (14-DAP) is a labdane diterpene isolated from
Andrographis paniculata with previously reported calcium channel blocking
activity. Its potential platelet activating factor (PAF) antagonistic activity
in bovine neutrophils was assessed. 14-DAP, in concentrations between 10-100
microM, reduced the extracellular acidification rate and the intracellular
alkalinization in a dose-dependent manner. In addition, 14-DAP reduced
PAF-induced calcium flux in the presence of extracellular calcium, and tyrosine
phosphorylation of a 44 kDa protein corresponding to the MAPK(ERK1). However,
14-DAP reduced the 3H-PAF binding with a Ki of 7.8 x 10 (- 9)M, and a Hill slope
of 0.63, suggesting that there is more than one binding site for 14-DAP. We
concluded that 14-DAP is an effective antagonist of PAF-mediated processes in
bovine neutrophils, probably by virtue of its calcium channel blocking property.

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

PMID: 16041644 [PubMed - indexed for MEDLINE]

33: Phytomedicine. 2005 Jun;12(6-7):403-9.

A phase I clinical study of Andrographis paniculata fixed combination Kan Jang
versus ginseng and valerian on the semen quality of healthy male subjects.

Mkrtchyan A, Panosyan V, Panossian A, Wikman G, Wagner H.

Republican Medical Scientific Centre of Dermatology and Diseases Disseminated by
Sexual Contacts, Yerevan, Armenia.

The safety of different doses of Kan Jang--a fixed combination of Andrographis
paniculata special extract (SHA-10) and Acanthopanax senticosus--compared to two
extensively used medicinal plants, Valeriana officinalis and Panax ginseng in
the form of standardized extracts, has been examined. A phase I clinical study
was designed to evaluate the effect on semen quality of healthy males in terms
of spermatogenesis and quality of semen. The results of the study revealed no
significant negative effect of Kan Jang on male semen quality and fertility, but
rather a positive trend with respect to the number of spermatozoids in the whole
ejaculate, the percentage of active (normokinetic) forms of spermatozoids, and
fertility indexes, together with a decrease in the percentage of inactive
(diskinetic) forms of spermatozoids. In the group receiving ginseng, no
significant negative effects on the fertility parameters were revealed and there
was a clear decrease in the percentage of diskinetic forms of spermatozoids.
Subjects receiving valerian showed a temporary increase in the percentage of
normokinetic spermatozoids and a decrease in diskinetic forms, but these changes
had no effect on fertility indices. The results indicate that Kan Jang, ginseng
and valerian are safe with respect to effects on human male sterility when
administered at dose levels corresponding to approximately 3 times the human
daily dose.

Publication Types:
Clinical Trial
Clinical Trial, Phase I
Randomized Controlled Trial

PMID: 16008115 [PubMed - indexed for MEDLINE]

34: J Cell Biochem. 2005 Aug 1;95(5):970-8.

Andrograpanin, a compound isolated from anti-inflammatory traditional Chinese
medicine Andrographis paniculata, enhances chemokine SDF-1alpha-induced
leukocytes chemotaxis.

Ji LL, Wang Z, Dong F, Zhang WB, Wang ZT.

Department of Pharmacognosy, China Pharmaceutical University, 1 Shen Nong Road,
Nanjing, People's Republic of China.

Andrographis paniculata is a traditional Chinese medicine (TCM) that has been
effectively used for treatment of infection, inflammation, cold, fever, and
diarrhea in China. However, mechanism of its therapeutic function is not well
known. In the current study, we showed one of its components, andrograpanin,
could enhance chemokine stromal cell-derived factor-1alpha (SDF-1alpha) induced
chemotaxis in Jurkat and THP-1 cells. Further study demonstrated that this kind
of effect was CXC chemokine receptor-4 (CXCR4) specific, since andrograpanin
could not enhance other chemokines, such as RANTES, monocyte chemotactic
protein-1 (MCP-1), etc. induced cell chemotaxis. Mechanisms of andrograpanin
exerting its effect were not directly in the receptor and G protein coupling
level because it had no effect on the binding of SDF-1 to CXCR4, SDF-1 induced G
protein activation and adenyly cyclase inhibition. However, receptor
internalization might be involved, since we found it significantly reduced
SDF-1alpha-induced CXCR4 internalization. (c) 2005 Wiley-Liss, Inc.

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

PMID: 15937916 [PubMed - indexed for MEDLINE]

35: Planta Med. 2005 May;71(5):429-34.

Andrographolide inhibits IFN-gamma and IL-2 cytokine production and protects
against cell apoptosis.

Burgos RA, Seguel K, Perez M, Meneses A, Ortega M, Guarda MI, Loaiza A, Hancke
JL.

Laboratory of Molecular Pharmacology, Institute of Pharmacology, Faculty of
Veterinary Science, Universidad Austral de Chile, Valdivia, Chile.
rburgos1@uach.cl

Andrographolide is the main labdane diterpene present in Andrographis
paniculata. Two lines of evidence report immunostimulant and anti-inflammatory
properties for andrographolide in different models. Using murine T-cells in
vitro we demonstrated that andrographolide and to a lesser extent,
14-deoxyandrographolide (14-DAP), reduced significantly, in a dose-dependent
manner, the IFN-gamma production induced by concanavaline A (CON-A), with an
IC50 of 1.7 +/- 0.07 microM and 35.8 +/- 0.50 microM, respectively.
Andrographolide, but not 14-DAP, inhibited partially the IL-2 production induced
by CON-A. Andrographolide at doses of 5 and 10 microM reduced the
extracellular-signal-regulated protein kinase (ERK1/2) phosphorylation induced
by CON-A, whereas 14-DAP only reduced ERK1 and partially the ERK2
phosphorylation. The inhibition of ERK1/2 phosphorylation was associated to a
decrease in the IFN-gamma production, due that UO126, a specific ERK1/2
inhibitor, also reduced the IFN-gamma production in murine T-cells induced by
CON-A. Additionally, andrographolide and to a lesser extent 14-DAP, at doses of
50 microM and 100 microM, respectively, reduced the apoptosis induced by
hydrocortisone and PMA in thymocytes, which was associated to a decrease in
caspase-3 like activity. We conclude that both diterpenic labdanes isolated from
A. paniculata can exert potent immunosuppressant effects without affecting the
viability of the cells.

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

PMID: 15931581 [PubMed - indexed for MEDLINE]

36: J Pharm Biomed Anal. 2006 Jan 23;40(1):157-61.

Simultaneous determination of andrographolide and dehydroandrographolide in
Andrographis paniculata and Chinese medicinal preparations by microemulsion
electrokinetic chromatography.

Yanfang Z, Xingping L, Zongde Z, Liren C, Yongmin L.

Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou
730000, China.

The present paper describes the development of a microemulsion electrokinetic
chromatographic (MEEKC) method for simultaneous determination of andrographolide
and dehydroandrographolide in traditional Chinese medicines and Chinese
medicinal preparations. The MEEKC method involved the use of sodium dodecyl
sulfate (SDS) as surfactant, heptane as organic solvent and butan-1-ol as
co-solvent. The effect of temperature and pH of running buffers on separation
were examined. The optimized conditions (heptane 0.81% (w/w), SDS 3.31% (w/w),
butan-1-ol 6.61% (w/w) and 10mM sodium tetraborate buffer, pH 9.2) allowed a
useful and good reproducible separation of the studied analytes to be achieved.

PMID: 15894448 [PubMed - indexed for MEDLINE]

37: Nat Prod Res. 2005 Apr;19(3):223-30.

A new bis-andrographolide ether from Andrographis paniculata nees and evaluation
of anti-HIV activity.

Reddy VL, Reddy SM, Ravikanth V, Krishnaiah P, Goud TV, Rao TP, Ram TS, Gonnade
RG, Bhadbhade M, Venkateswarlu Y.

Natural Products Laboratory, Organic Chemistry Division-I, Indian Institute of
Chemical Technology, Hyderabad-500 007, India.

Novel bis-andrographolide ether (1) and six known compounds andrographolide,
14-deoxy-11,12-didehydroandrographolide, andrograpanin, 14-deoxyandrographolide,
(+/-)-5-hydroxy-7,8-dimethoxyflavanone, and 5-hydroxy-7,8-dimethoxyflavone have
been isolated from the aerial parts of Andrographis paniculata and their
structures were established by spectral data. All the isolates were tested for
the anti-HIV and cytotoxic activity.

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

PMID: 15702635 [PubMed - indexed for MEDLINE]

38: Br J Pharmacol. 2005 Mar;144(5):680-6.

Andrographolide interferes with binding of nuclear factor-kappaB to DNA in
HL-60-derived neutrophilic cells.

Hidalgo MA, Romero A, Figueroa J, Cortes P, Concha II, Hancke JL, Burgos RA.

Laboratory of Molecular Pharmacology, Institute of Pharmacology, Universidad
Austral de Chile, PO Box 567, Isla Teja s/n, Valdivia, Chile.

1. Andrographolide, the major active component from Andrographis paniculata, has
shown to possess anti-inflammatory activity. Andrographolide inhibits the
expression of several proinflammatory proteins that exhibit a nuclear factor
kappa B (NF-kappaB) binding site in their gene. 2. In the present study, we
analyzed the effect of andrographolide on the activation of NF-kappaB induced by
platelet-activating factor (PAF) and N-formyl-methionyl-leucyl-phenylalanine
(fMLP) in HL-60 cells differentiated to neutrophils. 3. PAF (100 nM) and fMLP
(100 nM) induced activation of NF-kappaB as determined by degradation of
inhibitory factor B alpha (IkappaB alpha) using Western blotting in cytosolic
extracts and by binding to DNA using electrophoretic mobility shift assay (EMSA)
in nuclear extracts. 4. Andrographolide (5 and 50 microM) inhibited the
NF-kappaB-luciferase activity induced by PAF. However, andrographolide did not
reduce phosphorylation of p38 MAPK or ERK1/2 and did not change IkappaB alpha
degradation induced by PAF and fMLP. 5. Andrographolide reduced the DNA binding
of NF-kappaB in whole cells and in nuclear extracts induced by PAF and fMLP. 6.
Andrographolide reduced cyclooxygenase-2 (COX-2) expression induced by PAF and
fMLP in HL-60/neutrophils. 7. It is concluded that andrographolide exerts its
anti-inflammatory effects by inhibiting NF-kappaB binding to DNA, and thus
reducing the expression of proinflammatory proteins, such as COX-2.

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

PMID: 15678086 [PubMed - indexed for MEDLINE]

39: Phytochem Anal. 2004 Nov-Dec;15(6):365-71.

Determination and variation of three active diterpenoids in Andrographis
paniculata (Burm.f.) Nees.

Pholphana N, Rangkadilok N, Thongnest S, Ruchirawat S, Ruchirawat M, Satayavivad
J.

Laboratory of Pharmacology, Chulabhorn Research Institute, Vibhavadee-Rangsit
Highway, Laksi, Bangkok 10210, Thailand.

Simple and rapid methods have been developed for the extraction and simultaneous
determination of the three active diterpenoids, andrographolide (AP1),
14-deoxy-11,12-didehydroandrographolide (AP3) and neoandrographolide (AP4), from
various samples of Andrographis paniculata (Burm.f.) Nees. Methanol extracts
from the dried leaves, stems and crude products were analysed by isocratic HPLC
using a methanol and water mobile phase with monitoring at 220 nm. There was a
large variation of the three active diterpenoids in different A. paniculata
products obtained from Thai markets. The results indicated that the amounts of
these active compounds consumed, based on the recommended daily doses, from
materials obtained from the different suppliers will be different. In addition,
the stability of these three active compounds was also examined in dry herbs
stored at room temperature. The results showed that andrographolide was more
stable than the others. In contrast, the content of
14-deoxy-11,12-didehydroandrographolide increased and the neoandrographolide
content fluctuated during storage time. The combination of different levels of
these compounds in the source materials and the changes during storage could
have a significant effect on the efficacy of this traditional herbal medicine in
clinical treatment.

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

PMID: 15595451 [PubMed - indexed for MEDLINE]

40: Zhong Xi Yi Jie He Xue Bao. 2004 Nov;2(6):456-8.

[Effect of ultra-fine powder technique on dissolution rates of andrographolide
and dehydroandrographolide in Andrographis paniculata]

[Article in Chinese]

Qiu RL, Li L, Li X, Zhang HX, Chen JW.

Department of Medicinal Chemistry, School of Pharmacy, Nanjing University of
Traditional Chinese Medicine, Nanjing, Jiangsu Province 210029, China.
rongliq@hotmail.com

OBJECTIVE: To investigate the effects of ultra-fine powder technique on
dissolution rates of the components in Andrographis paniculata. METHODS: High
performance liquid chromatography was employed to determine the concentration of
andrographolide and dehydroandrographolide in common powdered or ultra-fine
powdered Andrographis paniculata. RESULTS: The dissolution rates of
andrographolide and dehydroandrographolide in ultra-fine powdered Andrographis
paniculata were higher than those of the general powder. CONCLUSION: Ultra-fine
powder technique promotes the dissolution rates of andrographolide and
dehydroandrographolide.

Publication Types:
English Abstract

PMID: 15539030 [PubMed - indexed for MEDLINE]

41: Phytochem Anal. 2004 Sep-Oct;15(5):280-5.

Chemical fingerprinting of Andrographis paniculata using HPLC, HPTLC and
densitometry.

Srivastava A, Misra H, Verma RK, Gupta MM.

Central Institute of Medicinal and Aromatic Plants, PO CIMAP, Lucknow-226015,
India.

An attempt has been made to develop a method by which to determine the chemical
fingerprint of Andrographis paniculata (Acanthaceae). High-performance thin
layer chromatography (HPTLC) was used to analyse hexane, chloroform, methanol
and water extracts of leaves of A. paniculata. A computerised densitometer was
applied to the two-dimensional spectrographic image analysis of the HPTLC
plates. An HPLC equipped with a photodiode array detector was used for the
analyses of these different extracts. The analyses showed that andrographolide
and neoandrographolide are absent in the hexane extract but are present in
greater amounts in the methanol extract as compared with the other extracts.
These chromatograms may serve as a chemical fingerprint of the drug A.
paniculata for quality control purposes and in the preparation of formulations
based on the drug.

PMID: 15508831 [PubMed - indexed for MEDLINE]

42: J Ethnopharmacol. 2004 Dec;95(2-3):247-51.

Anti-malarial activity of some xanthones isolated from the roots of Andrographis
paniculata.

Dua VK, Ojha VP, Roy R, Joshi BC, Valecha N, Devi CU, Bhatnagar MC, Sharma VP,
Subbarao SK.

Malaria Research Centre, Sector III, BHEL, Hardwar 249 403, India.
virendradua@hotmail.com

Four xanthones were isolated from the roots of Andrographis paniculata using a
combination of column and thin-layer chromatographic methods. They were
characterized as (i) 1,8-di-hydroxy-3,7-dimethoxy-xanthone, (ii)
4,8-dihydroxy-2,7-dimethoxy-xanthone, (iii) 1,2-dihydroxy-6,8-dimethoxy-xanthone
and (iv) 3,7,8-trimethoxy-1-hydroxy xanthone by IR, MS and NMR spectroscopic
methods. In vitro study revealed that compound
1,2-dihydroxy-6,8-dimethoxy-xanthone possessed substantial anti-plasmodial
activity against Plasmodium falciparum with its IC(50) value of 4 microg ml(-1).
Xanthones bearing hydroxyl group at 2 position demonstrated most potent activity
while xanthones with hydroxyl group at 1,4 or 8 position possessed very low
activity. In vivo anti-malarial sensitivity test of this compound on Swiss
Albino mice with Plasmodium berghei infection using Peters' 4-day test gave
substantial reduction (62%) in parasitaemia after treating the mice with 30 mg
kg(-1) dose. In vitro cytotoxicity against mammalian cells revealed that
1,2-dihydroxy-6,8-dimethoxy-xanthone is non-cytotoxic with its IC(50) > 32
microg ml(-1).

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

PMID: 15507344 [PubMed - indexed for MEDLINE]

43: J Ethnopharmacol. 2004 Dec;95(2-3):205-8.

Screening for antihyperglycaemic activity in several local herbs of Malaysia.

Husen R, Pihie AH, Nallappan M.

School of Bioscience and Biotechnology, Faculty of Science and Technology,
Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia.

Screening of aqueous extract of Phyllantus niruri (PL), Zingiber zerumbet (ZG),
Eurycoma longifolia (TA-a and TA-b) and Andrographis paniculata (AP) to
determine their blood glucose lowering effect were conducted in normoglycaemic
and Streptozotocin-induced hyperglycaemic rats. Significant reduction in blood
glucose level at 52.90% was shown when hyperglycaemic rats were treated with 50
mg/kg body weight (BW) aqueous extract of AP. This effect is enhanced when
freeze-dried material was used, where 6.25 mg/kg BW gave 61.81% reduction in
blood glucose level. In the administration of TA-a and TA-b, positive results in
hyperglyacaemic rats were only obtained when 150 mg/kg BW of the aqueous extract
was used. No significant reduction in blood glucose level were shown in
hyperglycaemic rats treated with PL and ZG at all concentrations used (50, 100
and 150 mg/kg BW). In normoglycaemic rats, no significant reduction was noted
when all the same extracts were used.

Publication Types:
Comparative Study

PMID: 15507337 [PubMed - indexed for MEDLINE]

44: Phytochemistry. 2004 Aug;65(16):2317-21.

Flavonoids and andrographolides from Andrographis paniculata.

Koteswara Rao Y, Vimalamma G, Rao CV, Tzeng YM.

Department of Applied Chemistry, Chaoyang University of Technology, 168 Gifeng
E. Road, Wufeng, Taichung 413, Taiwan.

Two flavonoids, identified as 5,7,2',3'-tetramethoxyflavanone and
5-hydroxy-7,2',3'-trimethoxyflavone, as well as several other flavonoids,
andrographolide diterpenoids, and polyphenols, were obtained from the
phytochemical investigation of the whole plant of Andrographis paniculata, a
well known medicinal plant. The structures of these compounds were established
with the aid of spectroscopic methods, including analysis by 2D NMR
spectroscopy.

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

PMID: 15381002 [PubMed - indexed for MEDLINE]

45: J Pharmacol Exp Ther. 2005 Jan;312(1):366-72. Epub 2004 Aug 26.

Andrographolide interferes with T cell activation and reduces experimental
autoimmune encephalomyelitis in the mouse.

Iruretagoyena MI, Tobar JA, Gonzalez PA, Sepulveda SE, Figueroa CA, Burgos RA,
Hancke JL, Kalergis AM.

Departamento de Genetica Molecular y Microbiologia, Facultad de Ciencias
Biologicas, Pontificia Universidad Catolica de Chile, Alameda 340, Santiago,
Chile.

Andrographolide is a bicyclic diterpenoid lactone derived from extracts of
Andrographis paniculata, a plant indigenous to South Asian countries that shows
anti-inflammatory properties. The molecular and cellular bases for this
immunomodulatory capacity remain unknown. Here, we show that andrographolide is
able to down-modulate both humoral and cellular adaptive immune responses. In
vitro, this molecule was able to interfere with T cell proliferation and
cytokine release in response to allogenic stimulation. These results were
consistent with the observation that T cell activation by dendritic cells (DCs)
was completely abolished by exposing DCs to andrographolide during antigen
pulse. This molecule was able to interfere with maturation of DCs and with their
ability to present antigens to T cells. Furthermore, in vivo immune responses
such as antibody response to a thymus-dependent antigen and delayed-type
hypersensitivity were drastically diminished in mice by andrographolide
treatment. Finally, the ability of andrographolide to inhibit T cell activation
was applied to interfere with the onset of experimental autoimmune
encephalomyelitis (EAE), an inflammatory demyelinating disease of the central
nervous system that is primarily mediated by CD4(+) T cells and serves as an
animal model for human multiple sclerosis. Treatment with andrographolide was
able to significantly reduce EAE symptoms in mice by inhibiting T cell and
antibody responses directed to myelin antigens. Our data suggest that
andrographolide is able to efficiently block T cell activation in vitro, as well
as in vivo, a feature that could be useful for interfering with detrimental T
cell responses.

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

PMID: 15331658 [PubMed - indexed for MEDLINE]

46: Bioorg Med Chem Lett. 2004 Sep 20;14(18):4711-7.

Synthesis and structure-activity relationships of andrographolide analogues as
novel cytotoxic agents.

Nanduri S, Nyavanandi VK, Thunuguntla SS, Kasu S, Pallerla MK, Ram PS, Rajagopal
S, Kumar RA, Ramanujam R, Babu JM, Vyas K, Devi AS, Reddy GO, Akella V.

Discovery Chemistry, Dr. Reddy's Laboratories Ltd, Discovery Research, Bollaram
Road, Miyapur, Hyderabad 500 049, India. nandurisrinivas@drreddys.com

Andrographolide 1, the cytotoxic agent of the plant Andrographis paniculata was
subjected to semi-synthetic studies leading to the preparation of a number of
potent and novel analogues. Of the analogues synthesized, while 8,17-epoxy
andrographolide 6 retained the cytotoxic activity of 1, ester derivatives of 6
exhibited considerable improvement in activity. Lower activity was observed when
the epoxy moiety in the triacetate 9, derived from 6 was modified. Synthesis and
structure-activity relationships are discussed.

Publication Types:
Comparative Study

PMID: 15324893 [PubMed - indexed for MEDLINE]

47: J Ethnopharmacol. 2004 Jun;92(2-3):291-5.

Anticancer and immunostimulatory compounds from Andrographis paniculata.

Kumar RA, Sridevi K, Kumar NV, Nanduri S, Rajagopal S.

Discovery Research, Dr. Reddy's Laboratories, Miyapur, Hyderabad 500050, India.

Andrographis paniculata extract is traditionally used as a medicine to treat
different diseases in India, China and Southeast Asia. In the present study, we
evaluated the anticancer and immunomodulatory activity of the methanolic extract
of Andrographis paniculata in human cancer and immune cells. The methanolic
extract of Andrographis paniculata was fractionated into dichloromethane,
petroleum ether and aqueous extracts and screened for bioactivity. Our results
indicate that the dichloromethane fraction of the methanolic extract retains the
active compounds contributing for both the anticancer and immunostimulatory
activity. Dichloromethane fraction significantly inhibits the proliferation of
HT-29 (colon cancer) cells and augments the proliferation human peripheral blood
lymphocytes (HPBLs) at low concentrations. On further fractionation of the
dichloromethane extract we could isolate three diterpene compounds, i.e. [1]
andrographolide, [2] 14-deoxyandrographolide and [3]
14-deoxy-11,12-didehydroandrographolide. Andrographolide showed anticancer
activity on diverse cancer cells representing different types of human cancers.
Whereas all the three molecules showed enhanced proliferation and interleukin-2
(IL-2) induction in HPBLs.

PMID: 15138014 [PubMed - indexed for MEDLINE]

48: J Ethnopharmacol. 2004 Jun;92(2-3):281-9.

Inhibitory effect of some herbal extracts on adherence of Streptococcus mutans.

Limsong J, Benjavongkulchai E, Kuvatanasuchati J.

Department of Pharmacology, Faculty of Dentistry, Chulalongkorn University,
Henri-Dunant Road, Bangkok 10330, Thailand.

The objective of this study was to investigate the inhibitory effect of the
crude extracts from some herbs on adherence of Streptococcus mutans (S. mutans)
ATCC 25175 and TPF-1 in vitro. Six herbs, Andrographis paniculata; Cassia alata;
Chinese black tea (Camellia sinensis); guava (Psidium guajava); Harrisonia
perforata and Streblus asper, were extracted with 50 or 95% ethanol and dried.
Herbal extracted solution at 0.5% concentration (w/v) was initially tested for
bacterial adherence on glass surfaces. In order to identify type and effective
concentration of the extracts, the extracts that showed the inhibition on glass
surfaces were then tested on saliva-coated hydroxyapatite by the use of
radiolabeled bacteria. To study the mechanism of action, the effect of the
extracts at such concentration on glucosyltransferase and glucan-binding lectin
activities were examined. It was found that all extracts, but Streblus asper,
showed significant inhibitory effect on bacterial adherence to glass surfaces.
For the saliva-coated hydroxyapatite adherence assay, Andrographis paniculata,
Cassia alata, Chinese black tea and Harrisonia perforata could inhibit adherence
of S. mutans ATCC 25175. Chinese black tea was the strongest inhibitor followed
by Andrographis paniculata, Cassia alata and Harrisonia perforata, respectively.
For S. mutans TPF-1, adherence inhibition was observed from Andrographis
paniculata and Cassia alata at similar levels. The lowest concentrations of the
extracts that inhibited the adherence at least 50% were 0.5% of Andrographis
paniculata, 0.5% of Cassia alata, 0.3% of Chinese black tea and 0.5% of
Harrisonia perforata for S. mutans ATCC 25175. For S. mutans TPF-1, the
effective concentrations were 0.5% of Andrographis paniculata and 0.4% of Cassia
alata. All extracts at such concentrations decreased the activity of
glucosyltransferase from both strains. Only Andrographis paniculata and Cassia
alata eliminated or decreased the activity of glucan-binding lectin from both
strains. These findings suggested that Andrographis paniculata, Cassia alata,
Chinese black tea and Harrisonia perforata could inhibit adherence of S. mutans
ATCC 25175, while Andrographis paniculata and Cassia alata had an effect on S.
mutans TPF-1 in vitro at the concentrations employed in this study.

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

PMID: 15138013 [PubMed - indexed for MEDLINE]

49: Planta Med. 2004 Apr;70(4):293-8.

Andrographis paniculata in the treatment of upper respiratory tract infections:
a systematic review of safety and efficacy.

Coon JT, Ernst E.

Complementary Medicine, Peninsula Medical School, Universities of Exeter and
Plymouth, Exeter, UK. Jo.Thompson-Coon@pms.ac.uk

Acute respiratory infections represent a significant cause of over-prescription
of antibiotics and are one of the major reasons for absence from work. The
leaves of Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) are used
as a medicinal herb in the treatment of infectious diseases. Systematic
literature searches were conducted in six computerised databases and the
reference lists of all papers located were checked for further relevant
publications. Information was also requested from manufacturers, the spontaneous
reporting schemes of the World Health Organisation and national drug safety
bodies. No language restrictions were imposed. Seven double-blind, controlled
trials (n = 896) met the inclusion criteria for evaluation of efficacy. All
trials scored at least three, out of a maximum of five, for methodological
quality on the Jadad scale. Collectively, the data suggest that A. paniculata is
superior to placebo in alleviating the subjective symptoms of uncomplicated
upper respiratory tract infection. There is also preliminary evidence of a
preventative effect. Adverse events reported following administration of A.
paniculata were generally mild and infrequent. There were few spontaneous
reports of adverse events. A. paniculata may be a safe and efficacious treatment
for the relief of symptoms of uncomplicated upper respiratory tract infection;
more research is warranted.

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

PMID: 15095142 [PubMed - indexed for MEDLINE]

50: Biochem Pharmacol. 2004 Apr 1;67(7):1337-45.

Andrographolide suppresses endothelial cell apoptosis via activation of
phosphatidyl inositol-3-kinase/Akt pathway.

Chen JH, Hsiao G, Lee AR, Wu CC, Yen MH.

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei
114, Taiwan, ROC. jhchen@ndmctsgh.edu.tw

Andrographolide (Andro), an active component isolated from the Chinese official
herbal Andrographis paniculata, which has been reported to prevent oxygen
radical production and thus prevent inflammatory diseases. In this study, we
investigated the molecular mechanisms and signaling pathways by which Andro
protects human umbilical vein endothelial cells (HUVECs) from growth factor (GF)
deprivation-induced apoptosis. Results demonstrated that HUVECs undergo
apoptosis after 18 hr of GF deprivation but that this cell death was suppressed
by the addition of Andro in a concentration-dependent manner (1-100 microM).
Andro suppresses the mitochondrial pathway of apoptosis by inhibiting release of
cytochrome c into the cytoplasm and dissipation of mitochondrial potential
(Deltapsi(m)), as a consequence, prevented caspase-3 and -9 activation.
Treatment of endothelial cells with Andro-induced activation of the protein
kinase Akt, an anti-apoptotic signal, and phosphorylation of BAD, a down-stream
target of Akt. Suppression of Akt activity by wortmannin, by LY-294002 and by
using a dominant negative Akt mutant abolished the anti-apoptotic effect of
Andro. In contrast, the ERK1/2 activities were not affected by Andro. The ERK1/2
inhibitor, PD98059 failed to antagonize the protective effect of Andro. In
conclusion, Andro exerts its anti-apoptotic potential via activation of the
Akt-BAD pathway in HUVECs and thus may represent a candidate of therapeutic
agent for atherosclerosis.

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

PMID: 15013849 [PubMed - indexed for MEDLINE]

51: Phytother Res. 2004 Jan;18(1):47-53.

Comparative controlled study of Andrographis paniculata fixed combination, Kan
Jang and an Echinacea preparation as adjuvant, in the treatment of uncomplicated
respiratory disease in children.

Spasov AA, Ostrovskij OV, Chernikov MV, Wikman G.

Research Institute of Pharmacology of Volgograd Medical Academy, Volgograd,
Russia.

A three-arm study comparing the efficacy of Kan Jang, a fixed herbal combination
containing standardized Andrographis paniculata (N.) SHA-10 extract, with
Immunal, a preparation containing Echinacea purpurea (L.) extract, in
uncomplicated common colds was carried out in 130 children aged between 4 and 11
years over a period of 10 days. The study was designed as an adjuvant treatment
of Kan Jang and Immunal with a standard treatment. The patients were assigned to
one of the three groups. In control group C; 39 patients received only standard
treatment. Kan Jang and Immunal were used as an adjuvant to this therapy in the
other two groups. Adjuvant group A; 53 patients treated with Kan Jang tablets
concomitant to standard treatment, and adjuvant control group B; 41 patients
treated with concomitant Immunal. It was found that the adjuvant treatment with
Kan Jang, was significantly more effective than Immunal, when started at an
early stage of uncomplicated common colds. The symptoms of the disease were less
severe in the Kan Jang group. The effect of Kan Jang was particularly pronounced
in two objective parameters, amount of nasal secretion g/day and nasal
congestion. Kan Jang also accelerated the recovery time, whereas Immunal did not
show the same efficacy. The use of standard medication was significantly less in
the Kan Jang adjuvant group than in either the Immunal or standard treatment
group. Kan Jang treatment was well tolerated and no side effects or adverse
reactions were reported. Copyright 2004 John Wiley & Sons, Ltd.

Publication Types:
Clinical Trial
Comparative Study
Randomized Controlled Trial

PMID: 14750201 [PubMed - indexed for MEDLINE]

52: Planta Med. 2003 Dec;69(12):1075-9.

Antihyperglycemic effect of andrographolide in streptozotocin-induced diabetic
rats.

Yu BC, Hung CR, Chen WC, Cheng JT.

Department of Pharmacology, College of Medicine, National Cheng Kung University,
Tainan City, Taiwan.

The antihyperglycemic action of andrographolide, an active principle in the
leaves of Andrographis paniculata (Burm. f.) Nees, was investigated in
streptozotocin-induced diabetic rats (STZ-diabetic rats). Oral treatment of
andrographolide decreased the plasma glucose concentrations of STZ-diabetic rats
in a dose-dependent manner. Similar treatment with andrographolide also
decreased the plasma glucose in normal rats and the maximal effect was more
marked than that in STZ-diabetic rats. Andrographolide at the effective dose
(1.5 mg/kg) significantly attenuated the increase of plasma glucose induced by
an intravenous glucose challenge test in normal rats. In the isolated soleus
muscle of STZ-diabetic rats, andrographolide enhanced the uptake of radioactive
glucose in a concentration-dependent manner. Moreover, the mRNA and protein
levels of the subtype 4 form of the glucose transporter (GLUT4) in soleus muscle
were increased after repeated intravenous administration of andrographolide in
STZ-diabetic rats for 3 days. These results suggest that andrographolide can
increase the glucose utilization to lower plasma glucose in diabetic rats
lacking insulin.

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

PMID: 14750020 [PubMed - indexed for MEDLINE]

53: J Clin Pharm Ther. 2004 Feb;29(1):37-45.

Andrographis paniculata in the symptomatic treatment of uncomplicated upper
respiratory tract infection: systematic review of randomized controlled trials.

Poolsup N, Suthisisang C, Prathanturarug S, Asawamekin A, Chanchareon U.

Department of Pharmacy, Faculty of Pharmacy, Silpakorn University,
Nakhon-Pathom, Thailand. nalinee@email.pharm.su.ac.th

OBJECTIVE: To assess the efficacy of Andrographis paniculata in the symptomatic
treatment of uncomplicated upper respiratory tract infection. METHODS:
Systematic review of the literature and meta-analysis of randomized controlled
trials. Mean difference in the reduction in symptom severity scores between
treatment and control groups was calculated to obtain an overall estimate of
effect. RESULTS: Four studies met our inclusion criteria and were reviewed. A
total of 433 patients reported in three trials were included in the statistical
analysis. Andrographis paniculata fixed combination with Acanthopanax senticosus
was more effective than placebo. The mean difference was 2.13 points (95% CI
1.00-3.26 points, P=0.0002) on the symptom severity score. The difference in
effects between A. paniculata and placebo was 10.85 points (95% CI 10.36-11.34
points, P<0.0001) in favour of A. paniculata. CONCLUSION: Current evidence
suggests that A. paniculata extract alone or in combination with A. senticosus
extract may be more effective than placebo and may be an appropriate alternative
treatment of uncomplicated acute upper respiratory tract infection.

Publication Types:
Comparative Study
Review

PMID: 14748896 [PubMed - indexed for MEDLINE]

54: J Exp Ther Oncol. 2003 May-Jun;3(3):147-58.

Andrographolide, a potential cancer therapeutic agent isolated from Andrographis
paniculata.

Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R.

Discovery Research, Dr. Reddy's Laboratories, Miyapur, Hyderabad, India-500050.
sriramrajagopal@drreddys.com

Andrographis paniculata plant extract is known to possess a variety of
pharmacological activities. Andrographolide, the major constituent of the
extract is implicated towards its pharmacological activity. We studied the
cellular processes and targets modulated by andrographolide treatment in human
cancer and immune cells. Andrographolide treatment inhibited the in vitro
proliferation of different tumor cell lines, representing various types of
cancers. The compound exerts direct anticancer activity on cancer cells by
cell-cycle arrest at G0/G1 phase through induction of cell-cycle inhibitory
protein p27 and decreased expression of cyclin-dependent kinase 4 (CDK4).
Immunostimulatory activity of andrographolide is evidenced by increased
proliferation of lymphocytes and production of interleukin-2. Andrographolide
also enhanced the tumor necrosis factor-alpha production and CD marker
expression, resulting in increased cytotoxic activity of lymphocytes against
cancer cells, which may contribute for its indirect anticancer activity. The in
vivo anticancer activity of the compound is further substantiated against B16F0
melanoma syngenic and HT-29 xenograft models. These results suggest that
andrographolide is an interesting pharmacophore with anticancer and
immunomodulatory activities and hence has the potential for being developed as a
cancer therapeutic agent.

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

PMID: 14641821 [PubMed - indexed for MEDLINE]

55: Fitoterapia. 2003 Dec;74(7-8):692-4.

Antimicrobial activity of Andrographis paniculata.

Singha PK, Roy S, Dey S.

Plant Biotechnology Laboratory, Biotechnology Department, Indian Institute of
Technology, Kharagpur 721 302, West Bengal, India.

The antimicrobial activity of aqueous extract, andrographolides and
arabinogalactan proteins from Andrographis paniculata were evaluated. The
aqueous extract showed significant antimicrobial activity, which may be due to
the combined effect of the isolated arabinogalactan proteins and
andrographolides.

PMID: 14630176 [PubMed - indexed for MEDLINE]

56: Zhong Yao Cai. 2000 Jun;23(6):366-8.

[Advances in the study of Andrographis paniculata (Burm.f.) Nees]

[Article in Chinese]

Zhang T.

Institute for Drug Control, Wuzhou City, Guangxi Province, 543000

Publication Types:
Review

PMID: 12934603 [PubMed - indexed for MEDLINE]

57: Drug News Perspect. 2001 Aug;14(6):353-63.

Herbal preparations as a source of hepatoprotective agents.

Ram VJ.

Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, India.

Mono- and polyherbal preparations with potent antihepatotoxic activity in
various liver disorders, made from traditionally used herbs with proven
efficacy, have been described. More than 700 mono- and polyherbal preparations
in the form of decoction, tincture, tablets and capsules from more than 100
plants are in clinical use. Some of the herbs--such as Silybum marianum,
Picrorhiza kurroa, Andrographis paniculata and Glycyrrhizae radix--are very
common in most of the polyherbal preparations. This review covers the
preparations of widely used herbs such as S. marianum, Schisandra chinensis,
Phyllanthus amarus, P. kurroa, A. paniculata, G. radix, Lycium chinense and
Cochlospermum tinctorium as hepatoprotectants and includes the mode of action of
these preparations. Some polyherbal preparations such as Livex, HD-03, Hepatomed
and Hepatoguard with proven efficacy are also described in this review. (c) 2001
Prous Science. All rights reserved.

PMID: 12813598 [PubMed]

58: Phytomedicine. 2003 May;10(4):271-85.

Double-blind, placebo-controlled, randomized, pilot clinical trial of
ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees,
with Eleutherococcus senticosus Maxim, Schizandra chinensis Bail. and
Glycyrrhiza glabra L. extracts in patients with Familial Mediterranean Fever.

Amaryan G, Astvatsatryan V, Gabrielyan E, Panossian A, Panosyan V, Wikman G.

Republican Children's FMF Center, Yerevan State Medical University, Yerevan,
Armenia.

Double blind, randomized, placebo controlled pilot study of ImmunoGuard--a
standardized fixed combination of Andrographis paniculata Nees., Eleutherococcus
senticosus Maxim., Schizandra chinensis Bail., and Glycyrrhiza glabra L. special
extracts standardized for the content of Andrographolide (4 mg/tablet),
Eleuteroside E, Schisandrins and Glycyrrhizin, was carried out in two parallel
groups of patients. The study was conducted in 24 (3-15 years of both genders)
patients with Familial Mediterranean Fever (FMF), 14 were treated with tablets
of series A (verum) and 10 patients received series B product (placebo). The
study medication was taken three times of four tablets daily for 1 month. Daily
dose of the andrographolide--48 mg. The primary outcome measures in physician's
evaluation were related to duration, frequency and severity of attacks in FMF
patients (attacks characteristics score). The patient's self-evaluation was
based mainly on symptoms--abdominal, chest pains, temperature, arthritis,
myalgia, erysipelas-like erythema. All of 3 features (duration, frequency,
severity of attacks) showed significant improvement in the verum group as
compared with the placebo. In both clinical and self evaluation the severity of
attacks was found to show the most significant improvement in the verum group.
Both the clinical and laboratory results of the present phase II (pilot)
clinical study suggest that ImmunoGuard is a safe and efficacious herbal drug
for the management of patients with FMF.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 12809357 [PubMed - indexed for MEDLINE]

59: Phytochemistry. 2003 Apr;62(8):1271-5.

A flavone and an unusual 23-carbon terpenoid from Andrographis paniculata.

Reddy MK, Reddy MV, Gunasekar D, Murthy MM, Caux C, Bodo B.

Natural Products Division, Department of Chemistry, Sri Venkateswara University,
Tirupati 517 502, India.

Phytochemical investigation of the roots and aerial parts of Andrographis
paniculata Nees yielded a new flavone, 5-hydroxy-7,2',6'-trimethoxyflavone and
an unusual 23-carbon terpenoid,
14-deoxy-15-isopropylidene-11,12-didehydroandrographolide together with five
known flavonoids and four known diterpenoids. The structures of these compounds
were determined on the basis of spectral and chemical studies. Copyright 2003
Elsevier Science Ltd.

PMID: 12648550 [PubMed - indexed for MEDLINE]

60: J Chromatogr A. 2003 Jan 10;984(1):147-51.

Separation of andrographolide and neoandrographolide from the leaves of
Andrographis paniculata using high-speed counter-current chromatography.

Qizhen D, Jerz G, Winterhalter P.

Institute of Food and Biological Engineering, Hangzhou University of Commerce,
Hangzhou 310035, China. qizhendu@hotmail.com

The bioactive diterpenes andrographolide and neoandrographolide from the leaves
of Andrographis paniculata NEES (Acanthaceae) were successfully separated by
counter-current chromatography. A single 280-min separation yielded 189 mg of
99.9% andrographolide and 9.5 mg of 98.5% neoandrographolide applying
water-methanol-ethyl acetate-n-hexane (2.5:2.5:4:1) solvent system. Structure
confirmation was done by electrospray MS, one-dimensional NMR experiments,
circular dichroism, optical rotation dispersion, and specific optical rotation
[alpha]D.

PMID: 12564684 [PubMed - indexed for MEDLINE]

61: Chem Pharm Bull (Tokyo). 2003 Jan;51(1):24-6.

Heat-accelerated degradation of solid-state andrographolide.

Lomlim L, Jirayupong N, Plubrukarn A.

Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences,
Prince of Songkla University, Thailand.

The stability of andrographolide, the major active diterpene lactone from
Andrographis paniculata (BURM. f.) WALL. ex NEES., was determined to show that,
while crystalline andrographolide was highly stable even at 70 degrees C (75%
relative humidity) over a period of 3 months, its amorphous phase degraded
promptly. Heat-accelerated conditions revealed second-order kinetics of the
decomposition with the rate constant at 25 degrees C (k(25 degrees C)) predicted
from the Arrhenius plot of 3.8 x 10(-6) x d(-1). The major decomposed product
under elevated temperature (70 degrees C, 75% relative humidity) is
14-deoxy-11,12-didehydroandrographolide.

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

PMID: 12520123 [PubMed - indexed for MEDLINE]

62: J Agric Food Chem. 2003 Jan 15;51(2):524-9.

p-Hydroxybenzoic acid alkyl esters in Andrographis paniculata herbs, commercial
extracts, and formulated products.

Li W, Sun Y, Joseph J, Fitzloff JF, Fong HH, van Breemen RB.

Program for Collaborative Research in the Pharmaceutical Sciences and Department
of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of
Illinois at Chicago, 833 S. Wood Street, Chicago, IL 60612, USA.

Analysis of two commercial extracts of Andrographis paniculata using
high-performance liquid chromatography (HPLC) with photodiode array absorbance
detection showed the presence of several unexpected compounds, which were
isolated and identified as methyl, ethyl, and propyl esters of p-hydroxybenzoic
acid by using high-resolution mass spectrometry and nuclear magnetic resonance.
Quantitative analysis using HPLC revealed the presence of 0.22% p-hydroxybenzoic
acid methyl ester (methlyparaben) in one commercial extract, and both 0.11%
p-hydroxybenzoic acid ethyl ester (ethylparaben) and 0.20% p-hydroxybenzoic acid
propyl ester (propylparaben) in a second commercial extract of A. paniculata.
Analyses of additional commercial products of A. paniculata in tablet form
purchased from Chicago pharmacies also showed the presence of methyl- and
ethylparabens. To determine whether these compounds were natural chemical
constituents of the plant, pharmacopoeial reference A. paniculata plant powder
as well as samples of authenticated A. paniculata plant materials collected from
Indonesia, Hong Kong, and mainland China were obtained and analyzed by
HPLC-tandem mass spectrometry (LC-MS-MS). LC-MS-MS analyses confirmed the
presence of trace concentrations (<0.0008% w/w) of p-hydroxybenzoic acid methyl
ester but no p-hydroxybenzoic acid ethyl or propyl esters in these plant
samples. The limits of detection of the LC-MS-MS assay for these compounds were
5 pg on-column and 5 ppb in the plant material. The levels of these
p-hydroxybenzoic acid esters measured in the commercial products of A.
paniculata suggest that they were introduced inadvertently during processing or
as artificial additives.

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

PMID: 12517121 [PubMed - indexed for MEDLINE]

63: Phytomedicine. 2002 Oct;9(7):598-605.

Effect of andrographolide and Kan Jang--fixed combination of extract SHA-10 and
extract SHE-3--on proliferation of human lymphocytes, production of cytokines
and immune activation markers in the whole blood cells culture.

Panossian A, Davtyan T, Gukassyan N, Gukasova G, Mamikonyan G, Gabrielian E,
Wikman G.

ExLab Laboratories of Armenian Drug Agency, Yerevan, Armenia. phanos@sci.am

The immunomodulatory properties of a diterpene lactone andrographolide and Kan
Jang--a standardized fixed combination of Andrographis paniculata extract SHA-10
and Eleutherococcus senticosus extract SHE-3 were investigated. Their role on
spontaneous and phytohemagglutinin (PHA)-induced proliferation of human
peripheral blood lymphocytes (PBL) and on production of interferon-gamma
(INF-gamma) and tumor necrosis factor-alpha (TNF-alpha) were determined in
vitro. Proliferation of PBL induced by PHA was enhanced by co stimulation with
andrographolide and Kan Jang. At the same time andrographolide and Kan Jang
inhibit spontaneous proliferation of PBL in vitro. These preparations also have
effect on the formation of INF-gamma, TNF-alpha and some immune activation
markers such as neopterin (Neo), beta-2-microglobulin (beta2MG), and soluble
receptor for interleukin-2 (sIL-2R or sCD25) in blood cells culture.
Andrographolide and Kan Jang stimulate the INF-gamma, Neopterin and beta2MG
formation, but do not have any significant effect on the production of INF-gamma
and Neopterin in PHA stimulated blood cells. An opposite effect on these immune
makers was observed in the PHA-stimulated blood cells: both andrographolide and
Kan Jang increase the formation of TNF-alpha and beta2MG in cultivated whole
blood cells. Thus, andrographolide and Kan Jang can have an in vitro effect on
the activation and proliferation of immunocompetent cells as well on the
production of key cytokines and immune activation markers. The results show an
overall higher effect of the fixed combination as compared with the equivalent
amount of the pure substance andrographolide. The data are consistent with
results from clinical studies of Kan Jang and contributed to a better
understanding of these results.

PMID: 12487323 [PubMed - indexed for MEDLINE]

64: Phytomedicine. 2002 Oct;9(7):589-97.

A double blind, placebo-controlled study of Andrographis paniculata fixed
combination Kan Jang in the treatment of acute upper respiratory tract
infections including sinusitis.

Gabrielian ES, Shukarian AK, Goukasova GI, Chandanian GL, Panossian AG, Wikman
G, Wagner H.

Erebuni, Medical Centre, Yerevan, Armenia.

A double blind, placebo-controlled, parallel-group clinical study was carried
out to evaluate the effect of an Andrographis paniculata (N.) extract SHA-10
fixed combination, Kan Jang, in the treatment of acute upper respiratory tract
infections, including sinusitis. Ninety-five individuals in the treatment group
and 90 individuals in the placebo group completed the study according to the
protocol. The medication was taken for 5 days. Temperature, headache, muscle
aches, throat symptoms, cough, nasal symptoms, general malaise and eye symptoms
were taken as outcome measures with given scores. The total score analysis
showed a highly significant improvement in the verum group versus the placebo.
This result applied to the group as a whole and to the sinusitis subgroups. The
individual symptoms of headache and nasal and throat symptoms together with
general malaise showed the most significant improvement while cough and eye
symptoms did not differ significantly between the groups. Temperature was
moderately reduced in the verum group. It can be concluded that Kan Jang has a
positive effect in the treatment of acute upper respiratory tract infections and
also relieves the inflammatory symptoms of sinusitis. The study drug was well
tolerated.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 12487322 [PubMed - indexed for MEDLINE]

65: J Ethnopharmacol. 2002 Oct;82(2-3):239-42.

The screening of extracts from Goniothalamus scortechinii, Aralidium
pinnatifidum and Andrographis paniculata for anti-malarial activity using the
lactate dehydrogenase assay.

Siti Najila MJ, Noor Rain A, Mohamad Kamel AG, Syed Zahir SI, Khozirah S, Lokman
Hakim S, Zakiah I, Azizol AK.

Herbal Medicine Research Centre, Institute for Medical Research, Jalan Pahang,
50588 Kuala Lumpur, Malaysia. siti_najila@hotmail.com

Goniothalamus scortechinii, Andrographis paniculata and Aralidium pinnatifidum
were selected for the study based on their ethnomedicinal values. They were
screened for anti-malarial activity towards Plasmodium falciparum in vitro using
the lactate dehydrogenase (LDH) assay. The crude extract of G. scortechinii
exhibited the most potent schizonticidal activity compared to the other
extracts. It is effective against both the chloroquine resistant isolate, Gombak
A and the sensitive strain, D10 of Plasmodium falciparum. Furthermore a better
IC(50) value was obtained against the resistant strain, (9 microg/ml) compared
to the sensitive strain, 40 microg/ml. When the crude extract was fractionated
into 3 fractions, the chloroform fraction yielded the best activity, exhibiting
equipotency against both strains of parasite used; IC(50) of 23.53 microg/ml
against Gombak A and 21.06 microg/ml against D10.

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

PMID: 12242001 [PubMed - indexed for MEDLINE]

66: Biol Pharm Bull. 2002 Sep;25(9):1169-74.

Suppression of NO production in activated macrophages in vitro and ex vivo by
neoandrographolide isolated from Andrographis paniculata.

Batkhuu J, Hattori K, Takano F, Fushiya S, Oshiman K, Fujimiya Y.

Experimental Station for Medicinal Plant Studies, Graduate School of
Pharmaceutical Sciences, Tohoku University, Sendai, Japan.

In this study, we investigated the in vitro and ex vivo suppressive effects of
Andrographis paniculata on nitric oxide (NO) production in mouse peritoneal
macrophages elicited by bacillus Calmette-Guein (BCG) and stimulated by
lipopolysaccharide (LPS). Incubation of BCG-induced macrophages with the
methanol extract of A. paniculata reduced LPS stimulated NO production. The
diterpene lactones andrographolide and neoandrographolide were isolated as
active components from the extract. These compounds suppressed NO production in
a concentration-dependent manner in the concentration range from 0.1 to 100
microM and their IC50 values were 7.9 and 35.5 microM. Neoandrographolide also
suppressed NO production by 35 and 40% when the macrophages were collected after
oral administration of neoandrographolide at doses of 5 and 25 mg/kg/d and LPS
stimulated NO production was examined. However, andrographolide did not reduce
NO production on oral administration at the same doses. These results indicate
that neoandrographolide, which inhibited NO production both in vitro and ex vivo
may play an important role in the use of A. paniculata as an anti-inflammatory
crude drug.

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

PMID: 12230111 [PubMed - indexed for MEDLINE]

67: Phytochem Anal. 2002 Jul-Aug;13(4):222-7.

Determination of andrographolide, deoxyandrographolide and neoandrographolide in
the Chinese herb Andrographis paniculata by micellar electrokinetic capillary
chromatography.

Zhao J, Yang G, Liu H, Wang D, Song X, Chen Y.

Department of Chemistry, Hebei University, Baoding 071002, People's Republic of
China.

In this paper a micellar electrokinetic capillary chromatographic (MEKC) method
has been developed for determining the active components (andrographolide,
deoxyandrographolide and neoandrographolide) in water:ethanol extracts of the
Chinese crude herb Andrographis paniculata and its preparations (Chuanxinlian
and Xiaoyan Lidan tablets). The optimum separation conditions were 15 mM sodium
dodecyl sulphate in 30 mM borate buffer (pH 9.5) with UV detection wavelength at
214 nm and a constant voltage of 16 kV. An HPLC method was employed in order to
validate the MEKC method with respect to separation efficiency, sensitivity,
linearity and repeatability. The two methods are shown to be complementary
because of their different selectivity and thus are very suitable for
cross-validation studies. The MEKC method is demonstrated to be more appropriate
for the analysis of the active compounds in A. paniculata in that it is easier
and less expensive to use and does not suffer from contamination of the
chromatographic column.

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

PMID: 12184176 [PubMed - indexed for MEDLINE]

68: Immunol Invest. 2002 May;31(2):137-53.

Increased tumor necrosis factor alpha (TNF-alpha) and natural killer cell (NK)
function using an integrative approach in late stage cancers.

See D, Mason S, Roshan R.

Center for Advanced Medicine, Encinitias, California 92024, USA.
darrylsee@cs.com

Natural products may increase cytotoxic activity of Natural Killer Cells (NK)
Tumor Necrosis Factor alpha (TNF-alpha) while decreasing DNA damage in patients
with late-stage cancer. Pilot studies have suggested that a combination of
Nutraceuticals can raise NK cell function and TNF-alpha alpha activity and
result in improved clinical outcomes in patients with late stage cancer. The
objective of the study is to determine if Nutraceuticals can significantly raise
NK function and TNF levels in patients with late stage cancer. After informed
consent was obtained, 20 patients with stage IV, end-stage cancer were evaluated
(one bladder, five breast, two prostate, one neuroblastoma, two non-small cell
lung, three colon, 1 mesothelioma, two lymphoma, one ovarian, one gastric, one
osteosarcoma). Transfer Factor Plus (TFP+, 3 tablets 3 times per day), IMUPlus
(non denatured milk whey protein, 40 gm/day); Intravenous (50 to 100 gm/day) and
oral (1-2 gm/day) ascorbic acid; Agaricus Blazeii Murill teas (10 gm/day);
Immune Modulator Mix (a combination of vitamin, minerals, antioxidants and
immune-enhancing natural products); nitrogenated soy extract (high levels of
genistein and dadzein) and Andrographis Paniculata (500 mg twice, daily) were
used. Baseline NK function by standard 4 h 51Cr release assay and TNF alpha and
receptor levels were measured by ELISA from resting and phytohemagglutinin (PHA)
stimulated adherent and non-adherent Peripheral Blood Mononuclear Cell (PBMC).
Total mercaptans and glutathione in plasma were taken and compared to levels
measured 6 months later. Complete blood counts and chemistry panels were
routinely monitored. As of a mean of 6 months, 16/20 patients were still alive.
The 16 survivors had significantly higher NK function than baseline (p < .01 for
each) and TNF-alpha levels in all four cell populations studied (p < .01 for
each). Total mercaptans (p < .01) and TNF-alpha receptor levels were
significantly reduced (p < .01). It was also observed that hemoglobin,
hematocrit and glutathione levels were significantly elevated. The only toxicity
noted was occasional diarrhea and nausea. The quality of life improved for all
survivors by SF-36 form evaluation. An aggressive combination of immunoactive
Nutraceuticals was effective in significantly increasing NK function, other
immune parameters and hemoglobin from PBMC or plasma in patients with late stage
cancers. Nutraceutical combinations may be effective in late stage cancers.
Clinical outcomes evaluations are ongoing.

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

PMID: 12148949 [PubMed - indexed for MEDLINE]

69: J Agric Food Chem. 2002 Jul 31;50(16):4662-5.

Mechanism of the superoxide scavenging activity of neoandrographolide - a
natural product from Andrographis paniculata Nees.

Kamdem RE, Sang S, Ho CT.

Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick,
New Jersey 08901-8520, USA.

It was hypothesized that neoandrographolide might scavenge free radicals by
donating the allylic hydrogen of the unsaturated lactone ring. It was found that
the stoichiometry of the reaction between neoandrographolide and superoxide
radical generated from KO(2) in DMSO was 2 to 1. One major reaction product was
isolated and determined to be a diacid formed by the opening of the lactone
ring. It was concluded that the antiradical activity of neoandrographolide
proceeded by hydrogen abstraction from carbon C-15. A reaction mechanism was
proposed.

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

PMID: 12137494 [PubMed - indexed for MEDLINE]

70: Indian J Exp Biol. 2001 Dec;39(12):1308-10.

An experimental study of some indigenous drugs with special reference to
hydraulic permeability.

Upadhyay L, Mehrotra A, Srivastava AK, Rai NP, Tripathi K.

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

The effect of commonly used indigenous drugs for hepatic disorders i.e.
Tinospora cordifolia, (Guduchi/Amrita), Andrographis paniculata (Kalmegha),
Picrorhiza kurroa (Kutki), Phyllantnus niruri (Bhoomyamalaki) and Berberis
aristata (Daruharidra) was tested on the hydraulic permeability of water in the
presence of bile salt through a transport cell model. The data on hydraulic
permeability were calculated as t (time). JV = Lp x AP, where Lp = hydraulic
conductivity and AP is the pressure difference. It was observed that the value
of controlled hydraulic permeability (0.49 x 10(-8) M3 S(-1) N(-1)) decreased in
the presence of indigenous drugs and bile salt. The results suggest that these
drugs might have the cell membrane stabilizing property which may lead to
prevention of the toxic effect of bile salts in various hepatic disorders.

PMID: 12018531 [PubMed - indexed for MEDLINE]

71: Indian J Exp Biol. 2001 Jul;39(7):715-8.

Efficacy of crude extracts of Andrographis paniculata nees. on Callosobruchus
chinensis L. during post harvest storage of cowpea.

Bright AA, Babu A, Ignacimuth S, Dorn S.

Entomology Research Institute, Loyola College, Chennai, India.

Bioefficacy of different solvent fractions of A. paniculata was tested against
the cowpea weevil, C. chinensis in terms of its effect on adult mortality, total
egg output and emergence of F1 adults. All the extracts were effective against
the weevil, the efficacy was however more significant with respect to methanol
and ethyl acetate extracts at the highest concentrations (1,000 ppm) which lead
to 72.01 and 67.69% adult mortality respectively. The efficacy was dose
dependent. Total egg and percent emergence of Fl adults were lowest for methanol
followed by ethyl acetate fractions. Possible role of the principal chemical
constituents of this plant in bringing about mortality of the pest, reduction in
egg laying and adult emergence are discussed.

PMID: 12019768 [PubMed - indexed for MEDLINE]

72: Br J Pharmacol. 2002 Jan;135(2):399-406.

Andrographolide prevents oxygen radical production by human neutrophils:
possible mechanism(s) involved in its anti-inflammatory effect.

Shen YC, Chen CF, Chiou WF.

National Research Institute of Chinese Medicine, 155-1, Li-Nung Street Section
2, Shih-Pai, Taipei 112, Taiwan.

We have reported that andrographolide (ANDRO), an active component of
Andrographis paniculata, inhibits inflammatory responses by rat neutrophils. To
further elucidate the possible mechanism(s) underlying the ANDRO's effect,
N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced adhesion and
transmigration of isolated peripheral human neutrophils were studied.
Pretreatment with ANDRO (0.1 - 10 microM) concentration-dependently prevented
fMLP-induced neutrophil adhesion and transmigration. We further examined the
up-expression of surface Mac-1 (CD11b/CD18), an essential integrin mediated in
neutrophil adhesion and transmigration. ANDRO pretreatment significantly
decreased fMLP-induced up-expression of both CD11b and CD18. Accumulation of
reactive oxygen species (ROS) as well as quick intracellular calcium
([Ca(++)](i)) mobilization induced by fMLP displays two important signalling
pathways in regulating the up-expression of Mac-1 by neutrophils. That ANDRO
pretreatment diminished fMLP-induced production of H(2)O(2) and O(2)*(-), but
failed to block that of [Ca(++)](i) mobilization suggested that the ROS but not
[Ca(++)](i) signalling could be modulated by ANDRO. To clarify whether ROS
production impeded by ANDRO could be an antagonism of fMLP binding,
phorbol-12-myristate-13-acetate (PMA), a direct protein kinase C (PKC)
activator, was introduced to activate ROS production. PMA triggered remarkable
ROS production and adhesion, and were partially reversed by ANDRO. This
indicated that a PKC-dependent mechanism might be interfered by ANDRO. We
conclude that the prevention of ROS production through, at least in part,
modulation of PKC-dependent pathway could confer ANDRO the ability to
down-regulate Mac-1 up-expression that is essential for neutrophil adhesion and
transmigration.

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

PMID: 11815375 [PubMed - indexed for MEDLINE]

73: Environ Technol. 2001 Oct;22(10):1147-54.

Heavy metal and nutrient concentration in soil and plants growing on a
metalliferous chromite minespoil.

Samantaray S, Rout GR, Das P.

Plant Physiology and Biochemistry Laboratory, Regional Plant Resource Centre,
Orissa, India.

Metal contamination in soil and plant samples from a chromite mine and its
adjoining regions was determined. The metal concentration varied in stem, leaf
and root of different tree species. In the case of shrubs, the highest
concentration of iron (18.5 mg kg(-1) was detected in the stem of Combretum
roxburghii. The concentration of aluminium varied from 1.8 - 5.3 mg kg(-1) dry
weight, whereas the nickel content was found to be the highest in the stem of
Calotropis gigantea. In the case of herbs, chromium concentration was highest
(60.9 mg kg(-1) dry weight) in Evovulus alsenoides and the lowest (18.8 mg
kg(-1) dry weight) in Andrographis paniculata. There was a significant
correlation observed between chromium in soil with the root of tree species like
Lagerstroemia parviflora, Madhuca longifolia, Anogeissus latifolia and Haldina
cordyfolia. Nickel in soil was significantly correlated with the stem and leaf
of all the tree species except Chlroxylon sweitenta. Iron in soil showed
correlation with the stem and leaf of Chloroxylon sweitenia. Among the shrubs
(Calotropis gigantea, Combretum roxburghii and Smilax zeylancia), chromium in
soil showed a correlation with the root. Nickel in soil was positively
correlated with the stem and leaf of Calotropis gigantea and Combretum
roxburghii. Among the herbs, chromium in the whole plant of Evolvulus alsenoids,
Solanum surattense and Phyllanthus fraternus showed significant positive
correlation with soil; nickel in Solanum surattense showed significant positive
correlation with soil. The positive correlation coefficient was observed between
iron in the whole plant and soil on Phyllanthus virgatus, Phyllanthus fraternus
and Andrographis paniculata. The above information would be useful for the
establishment of a vegetation cover on the minewaste heaps.

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

PMID: 11766037 [PubMed - indexed for MEDLINE]

74: J Chromatogr A. 2001 Sep 28;930(1-2):171-6.

Determination of bioactive diterpenoids from Andrographis paniculata by micellar
electrokinetic chromatography.

Cheung HY, Cheung CS, Kong CK.

Research Group for Bioactive Products, Department of Biology and Chemistry, City
University of Hong Kong, Kowloon. bhhonyum@cityu.edu.hk

The present paper describes the development of a micellar electrokinetic
chromatographic (MEKC) method for simultaneous determination of andrographolide,
deoxyandrographolide and neoandrographolide in ethanol extracts of Andrographis
paniculata. Separations were carried out in a fused-silica capillary tube with
UV detection at 214 nm. Good separation was achieved using a 20 mM borate
buffer, containing 20 mM sodium dodecyl sulphate and 10 mM sodium cholate,
adjusted to pH 8.3 at an operating voltage of 25 kV, temperature of 35 degrees C
and a hydrodynamic injection of 5 s. The method was validated with good
correlation coefficients obtained (0.9986-0.9989) while relative standard
deviation (RSD) of migration time was between 1.14 and 2.42. It is concluded
that this method could be used for speedy and accurate qualitative and
quantitative analysis of bioactive diterpenoids in andrographis herb and its
derived products.

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

PMID: 11681575 [PubMed - indexed for MEDLINE]

75: Acta Pharmacol Sin. 2000 Dec;21(12):1157-64.

Anti-diabetic property of ethanolic extract of Andrographis paniculata in
streptozotocin-diabetic rats.

Zhang XF, Tan BK.

Department of Pharmacology, Faculty of Medicine, National University of
Singapore, Singapore 117597, Singapore.

AIM: To investigate the anti-diabetic effect of a crude ethanolic extract of
Andrographis paniculata in normal and streptozotocin (STZ)-induced diabetic
rats. METHODS & RESULTS: Oral administration of the extract at different doses
(0.1, 0.2, and 0.4 g/body weight) significantly reduced the fasting serum
glucose level in STZ-diabetic rats compared to the vehicle (distilled water),
but not in normal rats. This effect was dose-dependent. A similar result was
seen with metformin (0.5 g/body weight). In the glucose tolerance test, an oral
administration of the extract at the same doses suppressed the elevated glucose
level in normal and diabetic rats, as did metformin. The effects were also
dose-respondent. In the long-term experiment, the extract (0.4 g/body weight),
metformin (0.5 g/body weight), and vehicle were given twice daily to diabetic
rats for 14 d. On d 15, fasting serum glucose levels were found to be
significantly lower in the extract- and metformin-treated groups (P < 0.001)
than in the vehicle-treated group. The mean food and water intakes over 14 days
were significantly lower in the extract-treated group (P < 0.05, P < 0.01,
respectively) and also in the metformin-treated group (both P < 0.001) when
compared to the vehicle-treated group. No significant change in insulin level
was observed among the 3 groups of diabetic rats. The extract, like metformin,
maintained the leptin levels after 14-d treatment, whereas this level was
significantly decreased (P < 0.05) in the vehicle-treated group. The activity of
hepatic glucose-6-phosphatase (G-6-Pase) was significantly reduced by the
extract as well as by metformin (both P < 0.05). No significant difference in
hepatic glycogen stores was noted among the 3 groups. The extract caused 49.8%
reduction of fasting serum triglyceride levels, compared to 27.7% with
metformin. However, neither the extract nor metformin significantly affected
serum cholesterol level. CONCLUSION: The ethanolic extract of A paniculata
possesses antidiabetic property. Its antidiabetic effect may be attributed at
least in part to increased glucose metabolism. Its hypotriglyceridemic effect is
also beneficial in the diabetic state.

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

PMID: 11603293 [PubMed - indexed for MEDLINE]

76: J Ethnopharmacol. 2001 Nov;78(1):79-84.

In vitro antifilarial effects of three plant species against adult worms of
subperiodic Brugia malayi.

Zaridah MZ, Idid SZ, Omar AW, Khozirah S.

Forest Research Institute Malaysia (FRIM), Kepong, 52109, Kuala Lumpur,
Malaysia.

Five aqueous extracts from three plant species, i.e., dried husks (HX), dried
seeds (SX) and dried leaves (LX) of Xylocarpus granatum (Meliaceae), dried stems
(ST) of Tinospora crispa (Menispermaceae) and dried leaves (LA) of Andrographis
paniculata (Acanthaceae) were tested in vitro against adult worms of subperiodic
Brugia malayi. The relative movability (RM) value of the adult worms over the
24-h observation period was used as a measure of the antifilarial activity of
the aqueous extracts. SX extract of X. granatum demonstrated the strongest
activity, followed by the LA extract of A. paniculata, ST extract of T. crispa,
HX extract and LX extract of X. granatum.

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

PMID: 11585692 [PubMed - indexed for MEDLINE]

77: Phytother Res. 2001 Aug;15(5):382-90.

Modulatory influence of Andrographis paniculata on mouse hepatic and
extrahepatic carcinogen metabolizing enzymes and antioxidant status.

Singh RP, Banerjee S, Rao AR.

Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University,
New Delhi-110067, India.

The effects of two doses (50 and 100 mg/kg body wt/day for 14 days) of an 80%
hydroalcohol extract of Andrographis paniculata and butylated hydroxyanisole
(BHA) were examined on drug metabolizing enzymes, antioxidant enzymes,
glutathione content, lactate dehydrogenase (LDH) and lipid peroxidation in the
liver of Swiss albino mice (6-8 weeks old). The effect of the extract and BHA
were also examined on lung, kidney and forestomach for the activities of
glutathione S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD)
and catalase. A significant increase in the levels of acid soluble sulphydryl
(-SH) content, cytochrome P450, cytochrome P450 reductase, cytochrome b5
reductase, GST, DTD and SOD were observed at both dose levels of extract
treatment while catalase, glutathione peroxidase and glutathione reductase (GR)
showed significant increases only at the higher dose in the liver. Both
Andrographis treated groups showed a significant decrease in activity of LDH and
malondialdehyde (MDA) formation. BHA treated mice showed a significant increase
in the levels of cytochrome b(5), GST, DTD, -SH content, GR and catalase in
liver; while LDH and MDA levels were reduced significantly compared with their
control values. In the lung, SOD, catalase and DTD, in the kidney catalase, DTD
and GST, and in the forestomach SOD and DTD showed a significant increase at
both dose levels of treatment. In BHA treated mice GST, DTD and catalase were
significantly induced in the lung and along with these enzymes SOD was also
induced in the kidney. In the case of the forestomach of BHA treated mice GST,
DTD and SOD were enhanced significantly. These findings indicate the
chemopreventive potential of Andrographis paniculata against chemotoxicity
including carcinogenicity. Copyright 2001 John Wiley & Sons, Ltd.

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

PMID: 11507728 [PubMed - indexed for MEDLINE]

78: Phytother Res. 2001 May;15(3):253-6.

Studies on psychopharmacological activity of Andrographis paniculata extract.

Mandal SC, Dhara AK, Maiti BC.

Division of Pharmacognosy, Department of Pharmaceutical Technology, Jadavpur
University, Calcutta 700 032, India.

Psychopharmacological studies were conducted on an extract of Andrographis
paniculata herbs. The extract exhibited a significant alteration in behaviour
pattern and a reduction in spontaneous motility. The extract also produced a
prolongation of the pentobarbitone-induced sleeping time and lowered the body
temperature in different experimental animal models. Copyright 2001 John Wiley &
Sons, Ltd.

PMID: 11351363 [PubMed - indexed for MEDLINE]

79: Phytother Res. 2001 May;15(3):235-9.

Andrographis paniculata (Ness) induces relaxation of uterus by blocking voltage
operated calcium channels and inhibits Ca(+2) influx.

Burgos RA, Aguila MJ, Santiesteban ET, Sanchez NS, Hancke JL.

Institute of Pharmacology, Faculty of Veterinary Science, Universidad Austral de
Chile, P.O. Box 567, Valdivia, Chile. rburgos1@uach.cl

The possible relaxation of uterine smooth muscle by Andrographis paniculata
dried extract via a blockade of voltage operated calcium channels was
investigated in rats. Uterine horns pretreated with oestradiol were incubated in
Ca(+2) -free Jalon's solution and stimulated with KCl (20-60 mM) in order to
produce depolarization of the membrane. The isometric contractile response to 1
mM or cumulative concentrations of CaCl2 were blockaded by 0.2, 0.4 and 0.8
mg/mL of A. paniculata. The maximum contractile response induced by
acetylcholine was moderately antagonized by A. paniculata. The possible blockade
of Ca(+2) entry by A. paniculata was evaluated with (45)Ca(+2) uptake in uterine
rings incubated with free-Ca(+2)-Ringer's solution high in K+ (KCl 40 mM). The
influx was completely blockaded with 0.4 mg/mL of A. paniculata. These results
strongly suggest that A. paniculata blockades voltage operated calcium channels
inhibiting the entry of Ca(+2) from the external medium. Copyright 2001 John
Wiley & Sons, Ltd.

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

PMID: 11351359 [PubMed - indexed for MEDLINE]

80: Indian J Exp Biol. 2001 Jan;39(1):41-6.

Hepatoprotective and antioxidant property of Andrographis paniculata (Nees) in
BHC induced liver damage in mice.

Trivedi NP, Rawal UM.

Zoology Department, Gujarat University, Ahmedabad 380009, India.

Andrographis paniculata (AP) treatment prevents BHC induced increase in the
activities of enzymes y-Glutamyl transpeptidase, glutathione-S-transferase and
lipid peroxidation. The activities of antioxidant enzymes like superoxide
dismutase, catalase, glutathione peroxidase and the levels of glutathione were
decreased following BHC effect. Administration of AP showed protective effects
in the activity of superoxide dismutase, catalase, glutathione peroxidase,
glutathione reductase as well the level of glutathione. The activity of lipid
peroxidase was also decreased. The result indicate antioxidant and
hepatoprotective action of A. paniculata.

PMID: 11349524 [PubMed - indexed for MEDLINE]

81: Drug Deliv. 2000 Oct-Dec;7(4):209-13.

Targeting of liposomal andrographolide to L. donovani-infected macrophages in
vivo.

Sinha J, Mukhopadhyay S, Das N, Basu MK.

Biomembrane and Medicinal Chemistry Division, Indian Institute of Chemical
Biology, Calcutta.

Despite the rapid development in medicinal and pharmaceutical technology, the
targeting of drugs to phagocytic cells in macrophage-related diseases still
remains a major unsolved problem. By using the mannosyl-fucosyl receptors on
macrophages, attempts were made to target antileishmanial drugs encapsulated in
mannosylated or fucosylated liposomes to treat experimental leishmaniasis in the
hamster model. Mannosylated liposomes were found to be more potent in delivering
antileishmanial drugs to phagocytic cells. Liposomes loaded with an indigenous
drug, andrographolide, a labdane diterpenoid isolated from Indian medicinal
plant Andrographis paniculata, were prepared and tested against experimental
leishmaniasis in a hamster model. Mannosylated liposomes loaded with the drug
were found to be most potent in reducing the parasitic burden in the spleen as
well as in reducing the hepatic and renal toxicity. In addition, mannosylated
drug-loaded liposome-treated animals showed a normal blood picture and splenic
tissue histoarchitecture when compared with those treated with free drug or
regular liposomal drug. Such a drug-vehicle formulation may be considered for
clinical trials.

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

PMID: 11195427 [PubMed - indexed for MEDLINE]

82: Phytomedicine. 2000 Oct;7(5):351-64.

Pharmacokinetic and oral bioavailability of andrographolide from Andrographis
paniculata fixed combination Kan Jang in rats and human.

Panossian A, Hovhannisyan A, Mamikonyan G, Abrahamian H, Hambardzumyan E,
Gabrielian E, Goukasova G, Wikman G, Wagner H.

Guelbenkian Research & Drug Quality Control Laboratory of ADMTA, Yerevan,
Armenia. phanos@sci.am

Validated analytical methods (HPLC, CE and GC-MS) for determining the amount of
andrographolide (AND) in the blood plasma of rats and human volunteers following
the oral administration of Andrographis paniculata extract (APE) and
Andrographis paniculata fixed combination Kan Jang tablets were developed and
used for the pharmacokinetic study. Andrographolide was quickly and almost
completely absorbed into the blood following the oral administration of APE at a
dose of 20 mg/kg body wt. in rats. Its bio-availability, however, decreased
four-fold when a 10-times-higher dose was used. Since a large part (55 %) of AND
is bound to plasma proteins and only a limited amount can enter the cells, the
pharmacokinetics of AND are described well by a one-compartment model. Renal
excretion is not the main route for eliminating AND. It is most likely intensely
and dose dependently metabolized. Following the oral administration of four Kan
Jang tablets (a single therapeutic dose, equal to 20 mg of AND) to humans,
maximum plasma levels of approximately 393 ng/ml (approx. 1.12 microM) were
reached after 1.5-2 hours, as quantified using a UV diode-array detection
method. Half-life and mean residence times were 6.6 and 10.0 hours,
respectively. AND pharmacokinetics in humans are explained well by an open
two-compartment model. The calculated steady state plasma concentration of AND
for multiple doses of Kan Jang (after the normal therapeutic dose regimen, 3 x 4
tablets/day, about 1 mg AND/kg body wt./day) was approximately 660 ng/ml
(approx. 1.9 microM), enough to reveal any anti-PAF effect, particularly after
drug uptake when the concentration of AND in blood is about 1342 ng/ml (approx.
3.8 microM, while for anti-PAF effect EC50 - 5 microM).

PMID: 11081986 [PubMed - indexed for MEDLINE]

83: Phytomedicine. 2000 Oct;7(5):341-50.

Double-blind, placebo-controlled pilot and phase III study of activity of
standardized Andrographis paniculata Herba Nees extract fixed combination (Kan
jang) in the treatment of uncomplicated upper-respiratory tract infection.

Melchior J, Spasov AA, Ostrovskij OV, Bulanov AE, Wikman G.

Hallehalsan, Clinic, Ulricehamn, Sweden. jan.melchior@swipnet.se

Two randomized double-blind, placebo-controlled parallel group clinical trials
were performed to investigate the effect of a standardized extract (SHA-10) of
Andrographis paniculata fixed combination (Kan jang) in the treatment of
uncomplicated upper-respiratory tract infections. 46 patients in the pilot study
and 179 patients in the phase III study completed the study according to the
protocol. Medication was taken three times daily for a minimum of 3 days and a
maximum of 8 days for the pilot study, and for exactly three days in the phase
III study. The primary outcome measures in the patients self-evaluation were:
related to pain in the muscle, cough, throat symptoms, headache, nasal symptoms
and eye symptoms and temperature. The physician's fixed score diagnosis was
based mainly on sign/symptoms: ears, nose, oral cavity, lymph glands-tonsils and
eyes. The total symptom score showed a tendency toward improvement in the pilot
study (p = 0,08), while both the total symptom score and total diagnosis score
showed highly significant improvement (p < or = 0.0006 resp. 0.003) in the verum
group as compared with the placebo. In both studies throat symptoms/signs, were
found to show the most significant improvement.

Publication Types:
Clinical Trial
Clinical Trial, Phase III
Randomized Controlled Trial

PMID: 11081985 [PubMed - indexed for MEDLINE]

84: Phytother Res. 2000 Sep;14(6):432-5.

Aspects of the male reproductive toxicity/male antifertility property of
andrographolide in albino rats: effect on the testis and the cauda epididymidal
spermatozoa.

Akbarsha MA, Murugaian P.

Department of Animal Science, School of Life Sciences, Bharathidasan University,
India.

Previous work has shown that Andrographis paniculata leaf, when fed to male
albino rats, causes the arrest of spermatogenesis. The present study was
undertaken to investigate whether andrographolide, one of the major constituents
of this plant, is responsible for such an effect. The compound was administered
to 3-month-old male Wistar albino rats at two dose levels, for 48 days.
Fertility tests, analysis of the counts, motility and abnormalities of the cauda
epididymidal spermatozoa, and histopathological-evaluation of the testis were
carried out. The results showed that sperm counts decreased, the spermatozoa
were not motile, and several of them possessed abnormalities. The seminiferous
epithelium was-thoroughly disrupted and in the seminiferous tubules, fully
differentiated spermatozoa were far too limited; cells in the divisional stages
were prevalent; multinucleate giant cells were abundant and Leydig cells
appeared intact. It is inferred that andrographolide could affect
spermatogenesis by preventing cytokinesis of the dividing spermatogenic cell
lines. The multinucleate giant cells are comparable to the symplasts generated
by cytochalasin-D and ursolic acid due to action at stages V-VII of the
spermatogenic cycle. Sertoli cell damage and spermatotoxic effects are also
apparent. Thus, the study points to a male reproductive toxic effect of this
compound when used as a therapeutic; the study also confirms the possible
prospective use of andrographolide in male contraception. Copyright 2000 John
Wiley & Sons, Ltd.

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

PMID: 10960897 [PubMed - indexed for MEDLINE]

85: Phytother Res. 2000 Aug;14(5):333-8.

A phase I trial of andrographolide in HIV positive patients and normal
volunteers.

Calabrese C, Berman SH, Babish JG, Ma X, Shinto L, Dorr M, Wells K, Wenner CA,
Standish LJ.

Bastyr University Research Institute, Bastyr University, Washington 98028, USA.
carlo@bastyr.edu

A phase I dose-escalating clinical trial of andrographolide from Andrographis
paniculata was conducted in 13 HIV positive patients and five HIV uninfected,
healthy volunteers. The objectives were primarily to assess safety and
tolerability and secondarily to assess effects on plasma virion HIV-1 RNA levels
and CD4(+) lymphocyte levels. No subjects used antiretroviral medications during
the trial. Those with liver or renal abnormalities were excluded. The planned
regimen was 5 mg/kg bodyweight for 3 weeks, escalating to 10 mg/kg bodyweight
for 3 weeks, and to 20 mg/kg bodyweight for a final 3 weeks. The trial was
interrupted at 6 weeks due to adverse events including an anaphylactic reaction
in one patient. All adverse events had resolved by the end of observation. A
significant rise in the mean CD4(+) lymphocyte level of HIV subjects occurred
after administration of 10 mg/kg andrographolide (from a baseline of 405
cells/mm(3) to 501 cells/mm(3); p = 0.002). There were no statistically
significant changes in mean plasma HIV-1 RNA levels throughout the trial.
Andrographolide may inhibit HIV-induced cell cycle dysregulation, leading to a
rise in CD4(+) lymphocyte levels in HIV-1 infected individuals. Copyright 2000
John Wiley & Sons, Ltd.

Publication Types:
Clinical Trial
Clinical Trial, Phase I

PMID: 10925397 [PubMed - indexed for MEDLINE]

86: J Ethnopharmacol. 2000 Jul;71(1-2):115-21.

Andrographis paniculata (Nees) selectively blocks voltage-operated calcium
channels in rat vas deferens.

Burgos RA, Imilan M, Sanchez NS, Hancke JL.

Institute of Pharmacology, Faculty of Veterinary Science, Universidad Austral de
Chile, P.O. Box 567, Valdivia, Chile. rburgos1@uach.cl

The possible blockade of voltage-operated calcium channels (VOCs) by
Andrographis paniculata dried extract in vas deferens smooth muscle was
investigated in rats. The tissues were incubated in Ca(2+)-free Kreb's solution
and stimulated with KCl (40 mM) to produce depolarisation of the membrane. The
isometric contractile response to cumulative concentrations of CaCl(2) was
effectively blockaded by 0.2 and 0.4 mg/ml A. paniculata. In other experiments,
the maximum contractile response induced by norepinephrine was not antagonised
by 0.2, 0.4 or 0.8 mg/ml A. paniculata. The possible blockade of Ca(2+) entry by
A. paniculata was evaluated with 45Ca(2+) uptake in vas deferens treated with
reserpine (5 and 2.5 mg/kg) 48 and 24 h before the experiments. Epididymal
segments were incubated with Ca(2+)-free Kreb's solution with KCl, 25 and 50 mM.
The influx was completely blockaded with 0.4 mg/ml A. paniculata. These results
suggest that A. paniculata selectively blockades VOCs, hence inhibiting the
45Ca(2+) influx.

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

PMID: 10904154 [PubMed - indexed for MEDLINE]

87: Planta Med. 2000 May;66(4):314-7.

Suppression of rat neutrophil reactive oxygen species production and adhesion by
the diterpenoid lactone andrographolide.

Shen YC, Chen CF, Chiou WF.

National Research Institute of Chinese Medicine, Taipei, Taiwan.

The present study was to examine whether andrographolide, a diterpenoid lactone
isolated from the anti-inflammatory herbal medicine Andrographis paniculata
(Burm. f.) Nees. (Acanthaceae), has the ability to prevent
phorbol-12-myristate-13-acetate (PMA)-induced reactive oxygen species (ROS)
production, as well as N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced
adhesion by rat neutrophils. Results demonstrated that PMA (100 ng/ml) induced
rapid accumulation of H2O2 and O2. in neutrophils within 30 minutes.
Andrographolide (0.1 to 10 microM) pretreatment (10 min, 37 degrees C)
significantly attenuated the accumulation of these two oxygen radical
metabolites. Administration of andrographolide also significantly prevented
fMLP-induced neutrophil adhesion. These data suggest that preventing ROS
production and neutrophils adhesion may confer andrographolide the ability to be
an anti-inflammatory drug.

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

PMID: 10865445 [PubMed - indexed for MEDLINE]

88: Clin Exp Pharmacol Physiol. 2000 May-Jun;27(5-6):358-63.

Antihyperglycaemic and anti-oxidant properties of Andrographis paniculata in
normal and diabetic rats.

Zhang XF, Tan BK.

Department of Pharmacology, Faculty of Medicine, National University of
Singapore, Singapore.

1. Oxidative stress is believed to be a pathogenetic factor in the development
of diabetic complications. In the present study, we investigated the ethanolic
extract of the aerial parts of Andrographis paniculata for antihyperglycaemic
and anti-oxidant effects in normal and streptozotocin-induced type I diabetic
rats. 2. Normal and diabetic rats were randomly divided into groups and treated
orally by gavage with vehicle (distilled water), metformin (500 mg/kg
bodyweight) or the extract (400 mg/kg bodyweight), twice a day for 14 days. 3.
At the end of the 14 day period, the extract, like metformin, significantly
increased bodyweight (P < 0.01) and reduced fasting serum glucose in diabetic
rats (P < 0.001) when compared with vehicle, but had no effect on bodyweight and
serum glucose in normal rats. Levels of liver and kidney thiobarbituric
acid-reactive substances (TBARS) were significantly increased (P < 0.0001, P <
0.01, respectively), while liver glutathione (GSH) concentrations were
significantly decreased (P < 0.005) in vehicle-treated diabetic rats. Liver and
kidney TBARS levels were significantly lower (P < 0.0001, P < 0.005,
respectively), whereas liver GSH concentrations were significantly higher (P <
0.05) in extract- and metformin-treated diabetic rats compared with
vehicle-treated diabetic rats. Andrographis paniculata significantly decreased
kidney TBARS level (P < 0.005) in normal rats. Hepatic superoxide dismutase
(SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were
significantly lower in vehicle-treated diabetic rats compared with
vehicle-treated normal rats. The extract, as well as metformin, significantly
increased the activity of SOD and CAT, but had no significant effect on GSH-Px
activity in diabetic rats. The extract and metformin did not produce significant
changes in the activity of these anti-oxidant enzymes in normal rats. 4. Our
results show that oxidative stress is evident in streptozotocin-diabetic rats
and indicate that the ethanolic extract of A. paniculata not only possesses an
antihyperglycaemic property, but may also reduce oxidative stress in diabetic
rats.

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

PMID: 10831236 [PubMed - indexed for MEDLINE]

89: Br J Pharmacol. 2000 Apr;129(8):1553-60.

Mechanisms of suppression of inducible nitric oxide synthase (iNOS) expression
in RAW 264.7 cells by andrographolide.

Chiou WF, Chen CF, Lin JJ.

National Research Institute of Chinese Medicine, Taipei, Taiwan.
wfchiou@cma23.nricm.edu.tw

Andrographolide, an active component found in leaves of Andrographis paniculata,
has been reported to exhibit nitric oxide (NO) inhibitory property in
endotoxin-stimulated macrophages, however, the detailed mechanisms remain
unclear. In the present study we investigated the effect of andrographolide on
the expression of inducible NO synthase (iNOS) mRNA, protein, and enzyme
activity in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS) plus
interferon-gamma (IFN-gamma). RAW 264.7 cells stimulated with LPS/IFN-gamma
activated NO production; in this condition andrographolide (1-100 microM)
inhibited NO production in a dose-dependent manner with an IC(50) value of
17.4+/-1.1 microM. Andrographolide also reduces the expression of iNOS protein
level but without a significant effect on iNOS mRNA. The reduction of iNOS
activity is thought to be caused by decreased expression of iNOS protein. In a
protein stability assay, andrographolide moderately but significantly reduced
the amount of iNOS protein as suggested by accelerating degradation.
Furthermore, andrographolide also inhibited total protein de novo synthesis as
demonstrated by [(35)S]-methionine incorporation. As a whole, these data suggest
that andrographolide inhibits NO synthesis in RAW 264.7 cells by reducing the
expression of iNOS protein and the reduction could occur through two additional
mechanisms: prevention of the de novo protein synthesis and decreasing the
protein stability via a post-transcriptional mechanism. It is also possible that
inhibition of iNOS protein expression and NO production under immune stimulation
and/or bacteria infection may explain, in part, the beneficial effects of
andrographolide as an anti-inflammatory agent.

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

PMID: 10780958 [PubMed - indexed for MEDLINE]

90: J Pharm Biomed Anal. 2000 May;22(4):705-9.

LC analysis of hepatoprotective diterpenoids from Andrographis paniculata.

Jain DC, Gupta MM, Saxena S, Kumar S.

Central Institute of Medicinal and Aromatic Plants, Lucknow, India.
cimap@technologist.com

PMID: 10768362 [PubMed - indexed for MEDLINE]

91: Phytomedicine. 1999 Oct;6(4):217-23.

Use of visual analogue scale measurements (VAS) to asses the effectiveness of
standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of
common cold. A randomized double blind-placebo study.

Caceres DD, Hancke JL, Burgos RA, Sandberg F, Wikman GK.

Facultad de Medicina, Universidad de Chile, Santiago, Chile.

The objective of our study was to measure the effectiveness of Andrographis
paniculata SHA-10 extract in reducing the prevalence and intensity of symptoms
and signs of common cold as compared with a placebo. A group of 158 adult
patients of both sexes completed the randomized double blind study in Valdivia,
Chile. The patients were divided in two equal size groups, one of which received
Andrographis paniculata dried extract (1200 mg/day) and the other a placebo
during a period of 5 days. Evaluations for efficacy were performed by the
patient at day 0, 2, and 4 of the treatment; each completed a self-evaluation
(VAS) sheet with the following parameters: headache, tiredness, earache,
sleeplessness, sore throat, nasal secretion, phlegm, frequency and intensity of
cough. In order to quantify the magnitude of the reduction in the prevalence and
intensity of the signs and symptoms of common cold, the risk (Odds Ratio = OR)
was calculated using a logistic regression model. At day 2 of treatment a
significant decrease in the intensity of the symptoms of tiredness (OR = 1.28;
95% CI 1.07-1.53), sleeplessness (OR = 1.71; 95% CI 1.38-2.11), sore throat (OR
= 2.3; 95% CI 1.69-3.14) and nasal secretion (OR = 2.51; 95% CI 1.82-3.46) was
observed in the Andrographis SHA-10 group as compared with the placebo group. At
day 4, a significant decrease in the intensity of all symptoms was observed for
the Andrographis paniculata group. The higher OR values were for the following
parameters: sore throat (OR = 3.59; 95% CI 2.04-5.35), nasal secretion (OR =
3.27; 95% CI 2.31-4.62) and earache (OR = 3.11; 95% CI 2.01-4.80) for
Andrographis paniculata treatment over placebo, respectively. It is concluded
that Andrographis paniculata had a high degree of effectiveness in reducing the
prevalence and intensity of the symptoms in uncomplicated common cold beginning
at day two of treatment. No adverse effects were observed or reported.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 10589439 [PubMed - indexed for MEDLINE]

92: Phytomedicine. 1999 Jul;6(3):157-61.

Effect of Andrographis paniculata extract on progesterone in blood plasma of
pregnant rats.

Panossian A, Kochikian A, Gabrielian E, Muradian R, Stepanian H, Arsenian F,
Wagner H.

Guelbenkian Research and DQCL of Armenian Drug Agensy, Yerevan, Armenia.
phanos@ipia.sci.am

The effect of the powdered extract of Andrographis paniculata leaves (APE), an
active principle of Kan Jang tablets [standardized for content of
andrographolide (4.6%) and 14-deoxo-andrographolide (2.3%) content (total
andrographolids--6.9%)] on blood progesterone content in rats was studied.
Peroral administration of APE during the first 19 days of pregnancy in doses of
200, 600, and 2000 mg/kg (i.e. doses 30, 90, and 300 fold higher than its daily
therapeutic dose in humans) does not exhibit any effect on the elevated level of
progesterone in the blood plasma of rats. Let us assume then that in therapeutic
dose, Andrographis paniculata extract cannot induce progesterone-mediated
termination of pregnancy.

PMID: 10439479 [PubMed - indexed for MEDLINE]

93: J Ethnopharmacol. 1999 Mar;64(3):249-54.

Antimalarial activity of extracts of Malaysian medicinal plants.

Najib Nik A Rahman N, Furuta T, Kojima S, Takane K, Ali Mohd M.

Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala
Lumpur, Malaysia.

In vitro and in vivo studies revealed that Malaysian medicinal plants, Piper
sarmentosum, Andrographis paniculata and Tinospora crispa produced considerable
antimalarial effects. Chloroform extract in vitro did show better effect than
the methanol extract. The chloroform extract showed complete parasite growth
inhibition as low as 0.05 mg/ml drug dose within 24 h incubation period
(Andrographis paniculata) as compared to methanol extract of drug dose of 2.5
mg/ml but under incubation time of 48 h of the same plant spesies. In vivo
activity of Andrographis paniculata also demonstrated higher antimalarial effect
than other two plant species.

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

PMID: 10363840 [PubMed - indexed for MEDLINE]

94: Zhongguo Zhong Xi Yi Jie He Za Zhi. 1997 Sep;17(9):547-9.

[Effects of Andrographis paniculata component on nitric oxide, endothelin and
lipid peroxidation in experimental atherosclerotic rabbits]

[Article in Chinese]

Wang HW, Zhao HY, Xiang SQ.

Department of Cardiovascular Diseases, Tongji Hospital, Tongji Medical
University, Wuhan.

OBJECTIVE: To observe the effects of Andrographis Paniculata component (API0134)
on nitric oxide (NO), endothelin (ET), cyclic guanosine monophosphate (cGMP),
lipid peroxide (LPO) and superoxide dismutase (SOD) in experimental
atherosclerotic rabbit. METHODS: An atherosclerotic rabbit model was established
by feeding high cholesterol diet supplemented by bovine serum albumin injection
bolus. The rabbits were randomly divided into the control, model, and API0134
treated group. Blood samples were collected before 4 weeks and 8 weeks after
relevent treatment. RESULTS: Before 4 and after 8 weeks API0134 administration,
compared with model group, the NO, cGMP and activity of SOD increased (P <
0.01), while LPO and ET decreased (P < 0.01). CONCLUSIONS: API0134 possesses the
effects of antioxidation, preserving endothelial function, and maintaining the
balance of NO/ET.

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

PMID: 10322878 [PubMed - indexed for MEDLINE]

95: Phytomedicine. 1999 Mar;6(1):27-31.

Inhibitory effect of andrographolide from Andrographis paniculata on PAF-induced
platelet aggregation.

Amroyan E, Gabrielian E, Panossian A, Wikman G, Wagner H.

Yerevan State Medical University, Armenia.

Andrographolide, an active principle of the Chinese drug Andrographis
paniculata, used for prevention and treatment of common cold in Scandinavia and
known as an antiinflammatory, antiviral, antithrombotic, hypotensive and
antiatherosclerotic drug, was investigated for its suggested influence on the
biosynthesis of eicosanoids and the platelet-activating factor (PAF). Whereas in
isolated human polymorph-nuclear leukocytes (PMNL) no influence on the
biosynthesis was found, it could be shown that andrographolide inhibits
PAF-induced human blood platelet aggregation in a dose dependent manner (IC50-5
microM). These results indicate that andrographolide has a mechanism of action
different from that of non-steroidal antiinflammatory drugs (NSAID) and most
likely associated with the cardiovascular and antithrombotic activity described
of Andrographis paniculata.

Publication Types:
In Vitro

PMID: 10228608 [PubMed - indexed for MEDLINE]

96: Pharmacol Res. 1998 Dec;38(6):413-7.

Cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide in the
anaesthetised rat and isolated right atria.

Zhang C, Kuroyangi M, Tan BK.

Department of Pharmacology, Faculty of Medicine, National University of
Singapore, Japan.

The cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide (DDA)
from Andrographis paniculata (Burm.f.) Nees (Acanthaceae) was elucidated in
anaesthetised Sprague-Dawley (SD) rats and isolated rat right atria. In
anaesthetised rats, DDA produced significant falls in mean arterial blood
pressure (MAP) and heart rate in a dose-dependent manner with the maximum
decrease of 37.6 +/- 2.6% and 18.1 +/- 4.8%, respectively. The ED50 value for
MAP was 3.43 mmol kg-1. Pharmacological antagonist studies were done using this
dose. The hypotensive action of DDA was not mediated through effects on the
alpha-adrenoceptor, muscarinic cholinergic and histaminergic receptors, for it
was not affected by phentolamine, atropine as well as pyrilamine and cimetidine.
However, it seems to work via adrenoceptors, autonomic ganglia receptor and
angiotensin-converting enzyme, since the hypotensive effect of DDA was negated
or attenuated in the presence of propranolol, hexamethonium and captopril. In
the isolated right atria, DDA caused negative chronotropic action and
antagonised isoproterenol-induced positive chronotropic actions in a
non-competitive and dose-dependent manner. These results further supported the
bradycardia-inducing and beta-adrenoceptor antagonistic properties of DDA in
vivo.

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

PMID: 9990649 [PubMed - indexed for MEDLINE]

97: Biochem J. 1999 Feb 15;338 ( Pt 1):107-13.

Inhibition of proprotein convertases-1, -7 and furin by diterpines of
Andrographis paniculata and their succinoyl esters.

Basak A, Cooper S, Roberge AG, Banik UK, Chretien M, Seidah NG.

Laboratories of Structure and Metabolism of Neuropeptides, Clinical Research
Institute, University of Montreal, Que, Canada. Basaka@ircm.umontreal.ca

Studies were performed to investigate the prohormone/proprotein convertase
(PC)-inhibitory properties of chemical constituents of the medicinally active
plant Andrographis paniculata (AP; from the family Acanthaceae), also known as
'King of Bitters'. Among the individual components tested against the clinically
important convertases, furin and PC1, neoandrographolide (a C3 O-glucoside
derivative of the major constituent andrographolide) exhibited the highest
inhibitory action with an IC50 of 53.5 microM against furin. The data further
revealed that although andrographolide, the major bitter principle of AP,
exhibited a relatively small enzyme inhibition (IC50=1.0 mM and Ki=200 microM
against furin), upon succinoylation, its inhibitory action against the above
convertases was enhanced significantly with a Ki in the low micromolar range
(<30 microM), suggesting that a specific structural modification of the
andrographolide skeleton may be exploited to develop a new class of non-peptide
inhibitors of PCs. When tested against PC7, these succinoylated derivatives of
andrographolide also displayed strong inhibitory action, with Ki values again in
the low micromolar range. This potentially interesting observation may be
attributed to the reported anti-HIV property of 14-dehydroandrographolide
succinic acid monoester (DASM). It is suggested here that DASM, by virtue of
this protease inhibitory property, possibly acts by suppressing the proteolytic
cleavage of envelope glycoprotein gp160 of HIV, which is known to be
PC-mediated, particularly by furin and PC7.

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

PMID: 9931305 [PubMed - indexed for MEDLINE]

98: Br J Pharmacol. 1998 Sep;125(2):327-34.

Andrographolide suppresses the expression of inducible nitric oxide synthase in
macrophage and restores the vasoconstriction in rat aorta treated with
lipopolysaccharide.

Chiou WF, Lin JJ, Chen CF.

National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC.

1. We investigated whether andrographolide, a diterpenoid lactone found at
Andrographis paniculata, influences the induction of the inducible nitric oxide
synthase (iNOS) in RAW264.7 cells activated by bacterial endotoxin (LPS), as
well as in the rats with endotoxic shock and in aortic rings treated with LPS.
2. Incubation of RAW264.7 cells with andrographolide (1 to 50 microM) inhibited
the LPS (1 microg ml(-1))-induced nitrite accumulation in concentration- and
time-dependent manners. Maximum inhibition was observed when andrographolide was
added together with LPS and decreased progressively as the interval between
andrographolide and LPS was increased to 20 h. 3. Western blot analysis
demonstrated that iNOS expression was markedly attenuated in the presence of
andrographolide for 6-24 h, suggesting that andrographolide inhibited iNOS
protein induction. 4. Thoracic aorta incubation with LPS (300 ng ml(-1)) for 5 h
in vitro exhibited a significant decrease in the maximal contractile response to
phenylephrine (10(-9)-10(-5) M). Andrographolide (30 microM) restored the
contractile response to control level. 5. In anaesthetized rats, LPS (10 mg
kg(-1), i.v.) caused a fall in mean arterial blood pressure (MAP) from 116+/-4
to 77+/-5mmHg. The pressor effect of phenylephrine (10 microg ml(-1), i.v.) was
also significantly reduced at 30, 60, 120 and 180 min after LPS injection. In
contrast, animals pretreated with andrographolide (1 mg kg(-1), i.v., 20 min
prior to LPS) maintained a significantly higher MAP when compared to LPS-rats
given with vehicle. Administration of andrographolide 60 min after LPS caused a
increase in MAP and significantly reversed the reduction of the pressor response
to phenylephrine. 6. Our results indicated that andrographolide inhibits nitrite
synthesis by suppressing expression of iNOS protein in vitro. And, this
inhibition of iNOS synthesis may contribute to the beneficial haemodynamic
effects of andrographolide in endotoxic shock.

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

PMID: 9786505 [PubMed - indexed for MEDLINE]

99: J Ethnopharmacol. 1997 Nov;58(3):219-24.

Testicular toxicity assessment of Andrographis paniculata dried extract in rats.

Burgos RA, Caballero EE, Sanchez NS, Schroeder RA, Wikman GK, Hancke JL.

Instituto de Farmacologia, Facultad de Ciencias Veterinarias, Universidad
Austral de Chile, Valdivia.

The possible testicular toxicity of Andrographis paniculata, Nees (Acanthaceae)
standardized dried extract was evaluated in male Sprague Dawley rats for 60
days. No testicular toxicity was found with the treatment of 20, 200 and 1000
mg/kg during 60 days as evaluated by reproductive organ weight, testicular
histology, ultrastructural analysis of Leydig cells and testosterone levels
after 60 days of treatment. It is concluded that Andrographis paniculata dried
extract did not produce subchronic testicular toxicity effect in male rats.

PMID: 9421258 [PubMed - indexed for MEDLINE]

100: J Ethnopharmacol. 1997 Apr;56(2):97-101.

Mechanisms of cardiovascular activity of Andrographis paniculata in the
anaesthetized rat.

Zhang CY, Tan BK.

Department of Pharmacology, Faculty of Medicine, National University of
Singapore, Singapore.

The cardiovascular activities of crude water extract (WE) of Andrographis
paniculata (Burm. f.) Nees (Acanthaceae), its three semi-purified ethyl acetate
(FA), n-butanol (FB) and aqueous (FC) fractions, as well as andrographolide, a
major plant constituent, were elucidated in anaesthetized Sprague-Dawley (SD)
rats for the very first time. FA and andrographolide, which possesses multiple
pharmacological activities, elicited no drop in mean arterial blood pressure
(MAP), while WE, FB and FC produced a significant fall in MAP in a
dose-dependent manner without significant decrease in heart rate. The ED50
values for WE, FB and FC were 11.4, 5.0 and 8.6 mg/kg-respectively. These
suggested that the hypotensive substance(s) of the crude water extract was
concentrated in FB. Pharmacological antagonist studies were consequently only
tested in FB (5 mg/kg). The hypotensive action of FB was not mediated through
effects on the beta-adrenoceptor, muscarinic cholinergic receptor and
angiotensin-converting enzyme, for it was not affected by propranolol, atropine
and captapril, respectively. However, it seems to work via alpha-adrenoceptors,
autonomic ganglion and histaminergic receptors, since the hypotensive effect of
FB was negated or attenuated in the presence of phentolamine, hexamethonium as
well as pyrilamine and cimetidine.

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

PMID: 9174969 [PubMed - indexed for MEDLINE]

101: Hindustan Antibiot Bull. 1997 Feb-Nov;39(1-4):56-60.

In vitro evaluation of inhibitory nature of extracts of 18-plant species of
Chhindwara against 3-keratinophilic fungi.

Qureshi S, Rai MK, Agrawal SC.

Department of Botany, Danielson College, Chhindwara, India.

Effect of extract of 18 plant species, viz., Acorus calamus, Adhatoda vasica,
Amomum subulatum, Andrographis paniculata, Boerhaavia diffusa, Cassia
occidentalis, Centella asiatica, Cymbopogon citratus, Hemidesmus indicus, Hyptis
suaveolens, Malvestrum sp., Passiflora edulis, Pergularia daemia, Peristrophe
bicalyculata, Shuteria hirsuta, Solanum nigrum, Tecoma stans, and Verbascum
chinense on the growth of Microsporum gypseum, Chrysosporium tropicum and
Trichophyton terrestre was evaluated and discussed. The sensitivity of the
keratinophilic fungi was evaluated by dry-weight method. The maximum inhibition
of mycelial growth was shown by M. gypseum (86.62%) followed by T. terrestre
(81.86%) and C. tropicum (74.06%) when treated with S. hirsuta whereas the
minimum inhibition was exhibited by M. gypseum (0.29%), C. tropicum (0.16%) and
T. terrestre (1.76%) when tested with the extract of P. edulis, A. vasica and B.
diffusa respectively.

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

PMID: 10386016 [PubMed - indexed for MEDLINE]

102: Clin Exp Pharmacol Physiol. 1996 Aug;23(8):675-8.

Hypotensive activity of aqueous extract of Andrographis paniculata in rats.

Zhang CY, Tan BK.

Department of Pharmacology, Faculty of Medicine, National University of
Singapore, Singapore.

1. The hypotensive activity of an aqueous extract of Andrographis paniculata was
studied using chronic intraperitoneal (i.p.) infusions by osmotic pumps. The
extract exhibited a dose-dependent hypotensive effect on the systolic blood
pressure (SBP) of spontaneously hypertensive rats (SHR). 2. The optimum
hypotensive dose determined was repeated in a study in SHR and their
normotensive controls, Wistar-Kyoto (WKY) rats, to demonstrate its comparative
effects on the SBP, plasma and lung angiotensin-converting enzyme (ACE)
activities, as well as on lipid peroxidation in the kidneys, as measured by the
thiobarbituric acid (TBA) assay. 3. The extract significantly lowered the SBP of
both SHR and WKY rats. 4. Plasma, but not lung, ACE activity and kidney TBA
level were significantly lower in extract-treated SHR when compared with
vehicle-treated SHR controls. 5. Plasma and lung ACE activities as well as
kidney TBA levels were not significantly different between extract- and
vehicle-treated WKY rats. 6. This study indicates that the aqueous extract of A.
paniculata lowers SBP in the SHR possibly by reducing circulating ACE in the
plasma as well as by reducing free radical levels in the kidneys. The
mechanism(s) of hypotensive action seems to be different in WKY rats.

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

PMID: 8886488 [PubMed - indexed for MEDLINE]

103: J Tongji Med Univ. 1996;16(4):193-7.

Protective effects of API0134 on myocardial ischemia and reperfusion injury.

Guo Z, Zhao H, Fu L.

Department of Internal Medicine, Tongji Hospital, Tongji Medical University,
Wuhan.

Previous studies have demonstrated that a crude extract from Chinese medicinal
herb Andrographis Paniculata Nees (APN) could prevent myocardial ischemia and
reperfusion injury. A refined extract API0134 was studied further. LAD was
ligated for 90 min in 20 dogs and then reperfused for 120 min. The animals were
randomly divided into 2 groups, API0134 treated group (n = 10), 45 min after
ischemia receiving a slow i.v. bolus of 1 mg/kg and then an infusion of 80
micrograms.kg-1/min for 60 min and control group (n = 10) which was given only
5% glucose in saline. Result showed that the hemodynamics in API0134 treated
group showed better effects of preventing the increase of the LVEDP and
maintaining relatively normal CO as compared with control group. Ischemic ECGs
were significantly milder. Malignant arrhythmia did not appear in API0134
treated group. After reperfusion, the infarct size was smaller (5.06 +/- 2.67%
vs 10.45 +/- 3.11%, P < 0.01), the damages found in myocardial ultrastructure
were significantly milder. It is concluded that API0134 may protect the
myocardium from ischemic reperfusion injury.

PMID: 9389078 [PubMed - indexed for MEDLINE]

104: J Med Assoc Thai. 1995 Jun;78(6):310-3.

The usage of Andrographis paniculata following Extracorporeal Shock Wave
Lithotripsy (ESWL).

Muangman V, Viseshsindh V, Ratana-Olarn K, Buadilok S.

Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol
University, Bangkok, Thailand.

One hundred consecutive cases with renal stones less than 3 cm in size and
normal renal function underwent ESWL from January to March 1994. Out of these,
50 were given Andrographis paniculata tablets (250 mg), 4 tablests tid, 25 were
given cotrimoxazole 2 tablets bid and 25 received norfloxacin 200 mg bid,
started immediately after ESWL and continued for 5 days. All tolerated the
treatment well and none had complications. At one month follow-up, pre- and
post-ESWL pyuria, hematuria and proteinuria among the Andrographis paniculata
group were 84, 58, 72, 40, 52, 22 per cent; the cotrimoxazole group 88, 64, 84,
64, 56, 44 per cent and the norfloxacin group 92, 56, 72, 40 per cent and 56, 28
per cent respectively. The results showed that post ESWL pyuria and hematuria in
patients receiving Andrographis peniculata were reduced to 0.69 and 0.55 time of
pre ESWL value. We think that this herbal medicine is beneficial in the
treatment of post ESWL urinary tract infection. Besides the herbal drug given to
eighteen previously sulfa sensitized patients resulted in no allergic reaction.

PMID: 7561556 [PubMed - indexed for MEDLINE]

105: J Tongji Med Univ. 1995;15(4):205-8.

An experimental study of the mechanism of andrographis paniculata nees (APN) in
alleviating the Ca(2+)-overloading in the process of myocardial ischemic
reperfusion.

Guo ZL, Zhao HY, Zheng XH.

Department of Medicine, Tongji Hospital, Tongji Medical University, Wuhan.

The aim of this experiment is to study the mechanism of APN in alleviating the
Ca(2+)-overloading in dog model during the process of ischemic reperfusion. In
comparison with the sustained ischemic group, the parameters in the ischemic
reperfusion group demonstrated: Ca(2+) of ischemic region of myocardial cell
increased (P < 0.05), Na+ increased remarkably (P < 0.01), the activity of
Ca(2+)-ATPase dropped remarkably (P < 0.01), and MDA increased significantly (P
< 0.01). Whereas in the group pretreated with APN, the Ca(2+) in the relevant
area reduced (P < 0.05), Na+ decreased significantly (P < 0.01), the activity of
Ca(2+)-ATPase and Na+-K+ ATPase increased remarkably (P < 0.01), and MDA
decreased significantly (P < 0.01). These findings indicate tha APN may improve
the activity of sarcolemma ATPase in alleviating the Ca(2+) and Na+ -overloading
by decreasing the harmful effect of oxygen free radicals.

Publication Types:
Comparative Study

PMID: 8731924 [PubMed - indexed for MEDLINE]

106: Chem Pharm Bull (Tokyo). 1994 Jun;42(6):1216-25.

Cell differentiation-inducing diterpenes from Andrographis paniculata Nees.

Matsuda T, Kuroyanagi M, Sugiyama S, Umehara K, Ueno A, Nishi K.

School of Pharmaceutical Sciences, University of Shizuoka, Japan.

The methanol extract of the aerial part of Andrographis paniculata Nees showed
potent cell differentiation-inducing activity on mouse myeloid leukemia (M1)
cells. From the ethyl acetate-soluble fraction of the methanol extract, six new
diterpenoids of ent-labdane type, 14-epi-andrographolide (3), isoandrographolide
(4), 14-deoxy-12-methoxyandrographolide (7),
12-epi-14-deoxy-12-methoxyandrographolide (8),
14-deoxy-12-hydroxyandrographolide (9) and 14-deoxy-11-hydroxyandrographolide
(10) as well as two new diterpene glucosides,
14-deoxy-11,12-didehydroandrographi-side (12) and 6'-acetylneoandrographolide
(14), and four new diterpene dimers, bis-andrograpolides A (15), B (16), C (17)
and D (18), were isolated along with six known compounds. The structures of the
diterpenoids were determined by means of spectral methods. Some of these
compounds showed potent cell differentiation-inducing activity towards M1 cells.

PMID: 8069972 [PubMed - indexed for MEDLINE]

107: Chin Med J (Engl). 1994 Jun;107(6):464-70.

Prevention of atherosclerotic arterial stenosis and restenosis after angioplasty
with Andrographis paniculata nees and fish oil. Experimental studies of effects
and mechanisms.

Wang DW, Zhao HY.

Cardiology Department, Tongji Hospital, Tongji Medical University, Wuhan.

Restenosis rate after coronary angioplasty has been up to 30%-40%. To solve this
problem, we studied the effects of Andrographis Paniculata Nees (APN) and fish
oil (FO, omega 3 polyunsaturated fatty acids over 70%) on atherosclerotic
stenosis and restenosis after experimental angioplasty and the relevant
mechanisms of APN and FO. Preliminary results showed that APN can significantly
alleviate atherosclerotic iliac artery stenosis induced by both
deendothelialization and high cholesterol diet (HCD) and restenosis following
angioplasty in rabbits. FO showed the same but milder effects than APN did. Both
APN and FO significantly inhibited blood monocytes to secrete growth factors in
vivo. Ca(++)-ATPase activity of cell membrane of atherosclerotic rabbits was
significantly decreased, while APN or FO, especially the former alleviated this
reduction. Refined extract of APN significantly decreased in vitro resting
platelet [Ca++]i and in vivo the resting and thrombin-stimulated platelet
[Ca++]i after oral administration of APN for 2 weeks. APN significantly
inhibited cell growth or DNA synthesis in dose-dependent manner. In conclusion
because of the mechanisms described above, APN can alleviate atherosclerotic
artery stenosis induced by both deendothelialization and HCD as well as lower
restenosis rate after experimental angioplasty. The effects of APN are evidently
superior to those of FO.

PMID: 7956489 [PubMed - indexed for MEDLINE]

108: Bangladesh Med Res Counc Bull. 1994 Apr;20(1):24-6.

Hypoglycaemic effects of Andrographis paniculata Nees on non-diabetic rabbits.

Borhanuddin M, Shamsuzzoha M, Hussain AH.

Dhaka Medical College, Bangladesh.

So far known Andrographis paniculata Nees (AP) is a hepatoprotective,
antiplatelet and antithrombotic drug. In this experiment its hypoglycaemic
effect has been tried in various way. Water extract of AP 10 mg/kg body weight
can prevent induction of hyperglycaemia significantly (P < 0.001) induced by
oral administration of glucose 2 mg/kg body weight. But any how failed to do so
in adrenaline induced hyperglycaemia. It also failed to demonstrate any "fasting
blood sugar lowering effect" upon chronic administration (6 weeks) of AP. So
probably AP prevents glucose absorption from gut. Whole experiment was done on
rabbits.

PMID: 7880153 [PubMed - indexed for MEDLINE]

109: Zhongguo Zhong Xi Yi Jie He Za Zhi. 1994 Jan;14(1):28-30, 34, 5.

[Study of Andrographis paniculata extracts on antiplatelet aggregation and
release reaction and its mechanism]

[Article in Chinese]

Zhang YZ, Tang JZ, Zhang YJ.

Tongji Hospital, Tongji Medical University, Wuhan.

63 patients of cardiac and cerebral vascular diseases were observed at 3 hours
and/or one week after taking Andrographis paniculata (AP) extracts. Results
showed that both 1 min. and 5 min. platelet aggregation induced by ADP were
significantly inhibited (P < 0.001), 33 cases of them were observed for one
week. The aggregation rate was even significantly lower than that of 3 hours.
Serotonin (5-HT) release reaction from platelet was observed in 20 volunteers
taking AP. Result showed 5-HT released from platelet decreased (P < 0.01), but
plasma 5-HT level remained unchanged. The ultrastructural observation showed
that AP could inhibit the releasing of dense and alpha agranules from platelet
and dilating of canalicular system. It suggested that a raise of platelet cAMP
level might be the mechanism of antiplatelet effect of AP.

Publication Types:
English Abstract

PMID: 8043997 [PubMed - indexed for MEDLINE]

110: J Tongji Med Univ. 1994;14(1):49-51.

The effect of andrographis paniculata nees (APN) in alleviating the myocardial
ischemic reperfusion injury.

Guo ZL, Zhao HY, Zheng XH.

Department of Cardiology, Tongji Hospital, Tongji Medical University, Wuhan.

In experimental dogs, the effect of APN in alleviating the ischemia-reperfusion
injury was prominent. Compared with the sustained ischemia group, superoxide
dismutase (SOD) in the ischemic region of myocardial tissue in the
ischemia-reperfusion group was significantly decreased and malondialdehyde (MDA)
markedly increased: Ca2+ in myocardial cells was increased; and ultrastructural
changes of myocardial tissues were severe. In the APN-pretreated
ischemia-reperfusion group, on the contrary, all the above parameters showed
reversely, i.e., SOD increased, MDA and intracellular Ca2+ decreased, the
ultrastructure changes were less distorted.

PMID: 7877195 [PubMed - indexed for MEDLINE]

111: J Ethnopharmacol. 1993 Oct;40(2):131-6.

Andrographolide protects rat hepatocytes against paracetamol-induced damage.

Visen PK, Shukla B, Patnaik GK, Dhawan BN.

ICMR Centre for Advanced Pharmacological Research on Traditional Remedies,
Central Drug Research Institute, Lucknow, India.

Andrographolide, the active constituent isolated from the plant Andrographis
paniculata, showed a significant dose dependent (0.75-12 mg/kg p.o. x 7)
protective activity against paracetamol-induced toxicity on ex vivo preparation
of isolated rat hepatocytes. It significantly increased the percent viability of
the hepatocytes as tested by trypan blue exclusion and oxygen uptake tests. It
completely antagonized the toxic effects of paracetamol on certain enzymes (GOT,
GPT and alkaline phosphatase) in serum as well as in isolated hepatic cells.
Andrographolide was found to be more potent than silymarin, a standard
hepatoprotective agent.

Publication Types:
Comparative Study

PMID: 8133653 [PubMed - indexed for MEDLINE]

112: Biochem Pharmacol. 1993 Jul 6;46(1):182-5.

Antihepatotoxic effects of major diterpenoid constituents of Andrographis
paniculata.

Kapil A, Koul IB, Banerjee SK, Gupta BD.

Department of Pharmacology, Regional Research Laboratory, Jammu, India.

The diterpenes andrographolide (I), andrographiside (II) and neoandrographolide
(III) isolated from Andrographis paniculata were investigated for their
protective effects on hepatotoxicity induced in mice by carbon tetrachloride or
tert-butylhydroperoxide (tBHP) intoxication. Pretreatment of mice with the
diterpenes (I, II & III; 100 mg/kg, i.p.) for 3 consecutive days produced
significant reduction in malondialdehyde formation, reduced glutathione (GSH)
depletion and enzymatic leakage of glutamic-pyruvate transaminase (GPT) and
alkaline phosphatase (AP) in either group of the toxin-treated animals. A
comparison with the known hepatoprotective agent silymarin revealed that I
exhibited a lower protective potential than II and III, which were as effective
as silymarin with respect to their effects on the formation of the degradation
products of lipid peroxidation and release of GPT and AP in the serum. GSH
status was returned to normal only by III. The greater protective activity of II
and III could be due to their glucoside groups which may act as strong
antioxidants.

Publication Types:
Comparative Study

PMID: 8347130 [PubMed - indexed for MEDLINE]

113: J Nat Prod. 1993 Jul;56(7):995-9.

Immunostimulant agents from Andrographis paniculata.

Puri A, Saxena R, Saxena RP, Saxena KC, Srivastava V, Tandon JS.

Division of Biochemistry, Central Drug Research Institute, Lucknow, India.

EtOH extract and purified diterpene andrographolides of Andrographis paniculata
(Acanthaceae) induced significant stimulation of antibody and delayed type
hypersensitivity (DTH) response to sheep red blood cells (SRBC) in mice. The
plant preparations also stimulated nonspecific immune response of the animals
measured in terms of macrophage migration index (MMI) phagocytosis of
14C-leucine labelled Escherichia coli and proliferation of splenic lymphocytes.
The stimulation of both antigen specific and nonspecific immune response was,
however, of lower order with andrographolide than with the EtOH extract,
suggesting thereby that substance(s) other than andrographolide present in the
extract may also be contributing towards immunostimulation.

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

PMID: 8377022 [PubMed - indexed for MEDLINE]

114: J Tongji Med Univ. 1993;13(4):193-8.

Experimental studies on prevention of atherosclerotic arterial stenosis and
restenosis after angioplasty with Andrographis Paniculata Nees and fish oil.

Wang DW, Zhao HY.

Cardiology Department, Tongji Hospital, Tongji Medical University, Wuhan.

In order to search for effective drugs to reduce restenosis incidence after
coronary angioplasty, we studied the effects of a Chinese herb, extract of
Andrographis Paniculata Nees (APN), and Fish Oil (FO) on atherosclerotic
stenosis and restenosis after experimental angioplasty. Preliminary results
showed that APN can significantly alleviate atherosclerotic iliac artery
stenosis induced by both deendothelialization and high cholesterol diet (control
group, stenosis incidence 100%, stenotic severe degree 60.53 +/- 31.03%, of
which 30% arteries (6) are total occlusion; FO group: stenotic incidence and
severe degree are 77% and 53.00 +/- 21.17%, respectively, and in APN group they
are 70% and 25.39 +/- 10.52%, respectively, P < 0.01), and follow-up angiography
4 weeks after angioplasty showed that dilated iliac arteries in control group
all had severe restenosis, but in APN group no or only mild restenosis occurs,
and in FO group restenosis is as severe as stenotic degree prior to angioplasty.
These preliminary results suggest that APN and FO can significantly alleviate
stenosis induced by deendothelialization and high cholesterol diet and
restenosis after angioplasty, while the former has a more marked effect. The
above findings lead the authors to conclude that APN may play an important role
in preventing restenosis after coronary angioplasty, but FO may be useful in
reducing the extent of of restenosis after coronary angioplasty.

PMID: 8151735 [PubMed - indexed for MEDLINE]

115: Toxicon. 1992 Oct;30(10):1131-42.

Plants with a reputation against snakebite.

Martz W.

Institute of Legal Medicine, Christian-Albrechts University, Kiel, F.R.G.

Many plants are recommended in traditional medicine as active against various
effects of snakebite. Few attempts have been made to investigate the veracity of
these assertions in controlled experiments. Several workers, mainly Oriental,
have investigated the reputation of such plants by performing in vitro and in
vivo experiments in order to demonstrate whether there was any protective
effect, using drugs or mixtures of drugs prepared using traditional formulae. In
some studies, these extracts were administered to mice before or after treatment
with different elapid or crotalid venoms. Other papers deal with selected
compounds isolated from Schumanniophyton magnificum, Eclipta prostrata or
Aristolochia shimadai, and their capacity to inhibit phospholipase A2 or other
enzymes (e.g. ATPase) or for physiological and biochemical properties (such as
effects on uterine tone or the protection of mitochondrial membranes). Japanese
workers have described the antihaemorrhagic effect of persimmon tannin from
Diospyros kaki. Atropine has been attributed a life-prolonging effect after
black mamba venom treatment. Prolonged survival was also observed after
pretreatment with extracts of Diodia scandens and Andrographis paniculata. Some
authors have found little or no beneficial effects. The papers collected so far
show that there are no systematic investigations in this field.

Publication Types:
Review

PMID: 1440620 [PubMed - indexed for MEDLINE]

116: Planta Med. 1992 Apr;58(2):146-9.

Choleretic effect of andrographolide in rats and guinea pigs.

Shukla B, Visen PK, Patnaik GK, Dhawan BN.

ICMR Centre for Advanced Pharmacological Research on Traditional Remedies,
Central Drug Research Institute, Lucknow, India.

Andrographolide from the herb Andrographis paniculata (whole plant) per se
produces a significant dose (1.5-12 mg/kg) dependent choleretic effect (4.8-73%)
as evidenced by increase in bile flow, bile salt, and bile acids in conscious
rats and anaesthetized guinea pigs. The paracetamol induced decrease in volume
and contents of bile was prevented significantly by andrographolide
pretreatment. It was found to be more potent than silymarin, a clinically used
hepatoprotective agent.

PMID: 1529026 [PubMed - indexed for MEDLINE]

117: Virology. 1992 Mar;187(1):56-62.

Mechanism of inhibition of HIV-1 infection in vitro by purified extract of
Prunella vulgaris.

Yao XJ, Wainberg MA, Parniak MA.

Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General
Hospital, Montreal, Quebec, Canada.

Crude extracts of four Chinese herbs, Arctium lappa, Astragalus membranaceus,
Andrographis paniculata, and Prunella vulgaris, were assessed in several tissue
culture lines for anti-HIV activity and for cytotoxicity. One extract, obtained
from P. vulgaris, was able to significantly inhibit HIV-1 replication with
relatively low cytotoxicity. The active factor was purified using sequential
precipitations with ethanol and n-butanol, followed by reverse-phase and gel
permeation high-performance liquid chromatographic separations. The active
component was anionic with a molecular weight of approximately 10 kDa. The
purified extract inhibited HIV-1 replication in the lymphoid cell line MT-4, in
the monocytoid cell line U937, and in peripheral blood mononuclear cells at
effective concentrations of 6, 30, and 12.5 micrograms/ml, respectively.
Pretreatment of uninfected cells with the extract prior to viral exposure did
not prevent HIV-1 infection. By contrast, preincubation of HIV-1 with the
purified extract dramatically decreased infectiousness. The purified extract was
also able to block cell-to-cell transmission of HIV-1, prevented syncytium
formation, and interfered with the ability of both HIV-1 and purified gp120 to
bind to CD4. PCR analysis confirmed the absence of HIV-1 proviral DNA in cells
exposed to virus in the presence of the extract. These results suggest that the
purified extract antagonizes HIV-1 infection of susceptible cells by preventing
viral attachment to the CD4 receptor.

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

PMID: 1371029 [PubMed - indexed for MEDLINE]

118: J Med Assoc Thai. 1991 Oct;74(10):437-42.

Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis in adults.

Thamlikitkul V, Dechatiwongse T, Theerapong S, Chantrakul C, Boonroj P, Punkrut
W, Ekpalakorn W, Boontaeng N, Taechaiya S, Petcharoen S, et al.

Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol
University, Bangkok.

One hundred and fifty-two adult patients with pharyngotonsillitis were enrolled
in the randomized double blind study to assess the efficacy of Andrographis
paniculata. The patients were randomized to receive either paracetamol or 3
g/day of Andrographis paniculata or 6 g/day of Andrographis paniculata for 7
days. The baseline characteristics of the patients among the three groups were
not different. The efficacy of paracetamol or high dose Andrographis paniculata
was significantly more than that of low dose Andrographis paniculata at day 3 in
terms of the relief of fever and sore throat. The clinical effects were not
different at day 7. Minimal and self limiting side effects were found in about
20 per cent in each group.

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

PMID: 1797953 [PubMed - indexed for MEDLINE]

119: Chin Med J (Engl). 1991 Sep;104(9):770-5.

Antithrombotic effects of Andrographis paniculata nees in preventing myocardial
infarction.

Zhao HY, Fang WY.

Department of Internal Medicine, Tongji Hospital, Tongji Medical University,
Wuhan.

In 16 dogs the endothelium of the left anterior descending coronary artery was
injured mechanically. Then a copper wire was inserted into the lumen as a choke
of flow and the vessel was slightly compressed from outside by a constrictor.
Eight dogs had been treated beforehand with a preparation of flavone extracted
from the root of the Chinese medicinal herb Andrographis paniculata (TFAP). In
the control group, saline solution was given, the epicardially recorded ST
segment started to elevate within 15 minutes, the platelet aggregation rate and
the plasma levels of TXB2 increased rapidly, whereas the level of 6-k-PGF1 alpha
remained stable. Platelet cGMP rose continuously; however, platelet cAMP rose
only at 60 minutes. Histological findings confirmed the occurrence of arterial
thrombus and myocardial necrosis. Contrariwise, in the pretreated group there
was no elevation of the ST segment, plasma 6-k-PGF1 alpha and platelet cAMP were
increased, the production of TXB2 and aggregation of platelets were inhibited,
and no thrombus or myocardial infarction was induced. All data suggest that TFAP
might promote the synthesis of PGI2, inhibit the production of TXA2, stimulate
the synthesis of cAMP in platelets, impede aggregation of platelets, and thereby
prevent the formation of thrombi as well as the development of myocardial
infarction.

PMID: 1935360 [PubMed - indexed for MEDLINE]

120: Proc Soc Exp Biol Med. 1991 May;197(1):59-66.

Dehydroandrographolide succinic acid monoester as an inhibitor against the human
immunodeficiency virus.

Chang RS, Ding L, Chen GQ, Pan QC, Zhao ZL, Smith KM.

Department of Medical Microbiology, University of California, Davis 95616.

Dehydroandrographolide succinic acid monoester (DASM) is the
dehydroandrographolyl ester of succinic acid; and andrographolide, from which
DASM is made, is the major diterpenoid lactone found in the Chinese medicinal
herb, Andrographis paniculata. DASM has been found to be an inhibitor against
the human immunodeficiency virus (HIV) in vitro. It was nontoxic to the H9 cell
at the concentrations of 50-200 (average, 108) micrograms/ml and was inhibitory
to the HIV-1 (IIIB) at the minimal concentration of 1.6-3.1 (average 2.0)
micrograms/ml. It was also inhibitory to two other strains of HIV-1 and a strain
of HIV-2. This inhibitory effect could also be demonstrated in cultures of
activated human blood mononuclear cells; the 50% toxic dose and the 50% HIV
inhibitory dose were about 200-greater than or equal to 400 and 0.8-2
micrograms/ml, respectively. At the subtoxic concentration, DASM partially
interfered with HIV-induced cell fusion and with the binding of HIV to the H9
cell. Presumably, it also interfered with HIV replication at another
unidentified step(s).

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

PMID: 1708503 [PubMed - indexed for MEDLINE]

121: Arch Pharm Res. 1991 Mar;14(1):93-5.

Hepatoprotective effects of Andrographis paniculata against carbon
tetrachloride-induced liver damage.

Rana AC, Avadhoot Y.

College of Pharmacy, Shri Govindram Seksaria Institute of Technology and
Science, Indore, India.

Alcoholic extract of the leaves of Andrographis paniculata Ness (= AAP) was
obtained by cold maceration. A dose of 300 mg/kg (1/6 of LD50) of the extract
was selected to study hepatoprotective action against carbon
tetrachloride-induced liver damage. The extract was found to be effective in
preventing liver damage which was evident by morphological, biochemical and
functional parameters.

PMID: 10319129 [PubMed - indexed for MEDLINE]

122: Indian J Med Res. 1990 Aug;92:284-92.

Hepatoprotective activity of andrographolide against galactosamine & paracetamol
intoxication in rats.

Handa SS, Sharma A.

Department of Pharmaceutical Sciences, Panjab University, Chandigarh.

Hepatoprotective effect of andrographolide (the major active diterpenoid lactone
of the plant Andrographis paniculata) was studied on acute hepatitis induced in
rats by single dose of galactosamine (800 mg/kg, ip)/paracetamol (3g/kg, po).
Hepatoprotective activity was monitored by estimating the serum transaminases
(GOT and GPT), alkaline phosphatase and bilirubin in serum, hepatic
triglycerides, and by histopathological changes in the livers of experimental
rats. Pre-treatment and/or post-treatment of rats at different time intervals
with different doses of andrographolide in the two experimental models of
hepatotoxicity showed that treatment of rats with 400 mg/kg, ip or 800 mg/kg,
po, 48, 24 and 2 h before galactosamine administration or with 200 mg/kg, ip, 1,
4 and 7 h after paracetamol challenge leads to complete normalisation of
toxin-induced increase in the levels of all the five biochemical parameters, and
significantly ameliorates toxin-induced histopathological changes in the livers
of experimental rats. The results confirmed the in vivo hepatoprotective effect
of andrographolide against galactosamine or paracetamol-induced hepatotoxicity
in rats. Since the protective effect of andrographolide was observed in two
types of intoxication, which are very different in their primary mechanism of
inducing hepatotoxicity, it is suggested that protective mechanisms of
andrographolide which are not specific to galactosamine or paracetamol toxicity
may be responsible for the hepatoprotective activity of the compound.

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

PMID: 2228075 [PubMed - indexed for MEDLINE]

123: Indian J Med Res. 1990 Aug;92:276-83.

Hepatoprotective activity of andrographolide from Andrographis paniculata
against carbontetrachloride.

Handa SS, Sharma A.

Department of Pharmaceutical Sciences, Panjab University, Chandigarh.

Andrographolide, a diterpenoid lactone, was isolated (yield 0.78% w/w) from A.
paniculata (whole plant). Its LD50 in male mice was 11.46 g/kg, ip.
Antihepatotoxic activity of andrographolide (100 mg/kg, ip) was compared with
861.33 mg/kg, ip, of the methanolic extract (equivalent to 100 mg/kg of
andrographolide) and 761.33 mg/kg ip, of the andrographolide-free methanolic
extract (equivalent to 861.33 mg/kg of the methanolic extract) of the plant,
using CCl4-intoxicated rats. Biochemical parameters like serum
transaminases--GOT and GPT, serum alkaline phosphatase, serum bilirubin and
hepatic triglycerides were estimated to assess the liver function. Overall
inhibition of CCl4-induced increase in the five biochemical parameters was found
to be 48.6 per cent (andrographolide), 32.0 per cent (methanolic extract) and
15.0 per cent (andrographolide-free methanolic extract). These biochemical
observations were supplemented by histopathological examination of the liver
slices. Further, andrographolide (100 mg/kg, ip) was found to normalize
completely the CCl4-induced increase in the pentobarbitone induced sleep time of
mice. The results suggest that andrographolide is the major active
antihepatotoxic principle present in A. paniculata.

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

PMID: 2228074 [PubMed - indexed for MEDLINE]

124: J Med Assoc Thai. 1990 Jun;73(6):299-304.

Undetectable anti-bacterial activity of Andrographis paniculata (Burma) wall. ex
ness.

Leelarasamee A, Trakulsomboon S, Sittisomwong N.

Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol
University, Bangkok.

Andrographis paniculata (Burma) Wall. ex Ness (AP) is a herbal medicine and has
been used for therapy of upper respiratory tract infection (URI) as well as
acute diarrhea with reported efficacy of 75-100 per cent. To investigate whether
anti-bacterial activity was responsible for the reported therapeutic success of
AP, we carried out a number of studies. The first study was a direct assay of
anti-bacterial activity of AP suspended in water. The tested pathogens included
Salmonella, Shigella, E.coli, gr. A Streptococci and S.aureus. Anti-bacterial
activity was not demonstrable even in a solution containing 25,000 mg per litre
of crude powder. The second was designed to detect serum bactericidal activity
after oral intake of stem and leaves of AP. Ten healthy volunteers were enrolled
in the study. They received a single oral dose of AP (1, 2, 3 and 6 g) in a
randomized, cross-over manner. The washout period was one week. Blood samples
were taken at 0, 1, 2, 4, 8 and 24 hours after ingestion. Serum bactericidal
activity was assayed by agar diffusion technique using Bacillus spores and five
strains of each pathogen (Shigella, Salmonella typhi, S.aureus and gr. A
Streptococci) incubated for 24 hours. Again serum bactericidal activity was not
detected in any of the sera tested. In a third study, ninety-six rats were daily
fed with high doses of AP ranging 0.12-24 g per kg body wt. for six months
before sacrifice. Antibacterial activity was still undetectable when lung
parenchyma and liver tissue was placed on culture media containing bacteria
tested. In conclusion, anti-bacterial activity of AP is undetectable in our
study.

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

PMID: 2230623 [PubMed - indexed for MEDLINE]

125: Indian J Exp Biol. 1990 May;28(5):421-6.

Antifertility effect of Andrographis paniculata (Nees) in male albino rat.

Akbarsha MA, Manivannan B, Hamid KS, Vijayan B.

Post-Graduate Department of Zoology, Jamal Mohamed College, Tiruchirapalli,
India.

Dry leaf powder of A. paniculata, when fed orally to male albino rats, at a dose
level of 20 mg powder per day for 60 days, resulted in cessation of
spermatogenesis, degenerative changes in the seminiferous tubules, regression of
Leydig cells and regressive and/or degenerative changes in the epididymis,
seminal vesicle, ventral prostate and coagulating gland. There was reduction in
the weight and fluid content of the accessory glands. The treatment also
resulted in accumulation of glycogen and cholesterol in the testis, and
increased activities of lactate dehydrogenase in testis and alkaline phosphatase
in testis and ventral prostate. The results suggest antispermatogenic and/or
antiandrogenic effect of the plant.

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

PMID: 2401516 [PubMed - indexed for MEDLINE]

126: Indian J Med Res. 1990 Apr;92:133-8.

In vitro studies on the effect of certain natural products against hepatitis B
virus.

Mehrotra R, Rawat S, Kulshreshtha DK, Patnaik GK, Dhawan BN.

ICMR Advance Centre for Pharmacological Research on Traditional Remedies,
Central Drug Research Institute, Lucknow.

Picroliv (active principle from Picrorrhiza kurroa), its major components
picroside I, catalpol, kutkoside I, kutkoside, andrographolide (active
constituent of Andrographis paniculata), silymarin and Phyllanthus niruri
extract were tested for the presence of anti hepatitis B virus surface antigen
(anti HBs) like activity. HBsAg positive serum samples obtained from hepatitis B
virus (HBV) associated acute and chronic liver diseases and healthy HBsAg
carriers were used to evaluate the anti-HBs like activity of compounds/extract.
The latter were mixed with serum samples and incubated at 37 degrees C overnight
followed by HBsAg screening in the Elisa system. A promising anti-HBsAg like
activity was noted in picroliv (and its major components) catalpol, P. niruri
which differed from the classical viral neutralization. Picroliv also inhibited
purified HBV antigens (HBsAg and HBsAg) prepared from healthy HBsAg carriers.
The in vitro testing system appears to be a suitable model to identify an agent
active against HBV, prior to undertaking detailed studies.

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

PMID: 2370093 [PubMed - indexed for MEDLINE]

127: J Tongji Med Univ. 1990;10(4):212-7.

Protective effects of andrographis paniculata nees on post-infarction myocardium
in experimental dogs.

Zhao HY, Fang WY.

Department of Internal Medicine, Tongji Hospital, Tongji Medical University,
Wuhan.

One hour after the development of myocardial infarction by formation of
thrombus, watery extract of Andrographis paniculata Nees (APN) was injected
intravenously to 7 dogs for observing the protective effect of this drug on
ischemic myocardium, 6 dogs served as control group. In the treated group PGI2
increased remarkably, synthesis of TXA2 was inhibited, cAMP in platelets was
elevated, CK-MB peak was lowered and appeared earlier, ELT was shortened,
release of platelet beta-GT was decreased, platelet maximum aggregation rate was
inhibited, the size of ischemic area recorded by epicardial ECG was reduced, the
amplitude of ST segment elevation was lower than that in the control group, Q
wave appeared in only one dog. Pathologically, the myocardial structure
surrounding the initially appearing ischemic area, i.e, the reversibly damaged
area, became relatively normal, while the degree of myocardial degeneration and
necrosis in the central part of the ischemic area was mild. These data suggest
that APN may limit the expansion of ischemic focus, exert marked protective
effect on reversibly ischemic myocardium and demonstrate a weak fibrinolytic
action.

PMID: 1965910 [PubMed - indexed for MEDLINE]

128: Chem Pharm Bull (Tokyo). 1989 Jul;37(7):1813-5.

Structure-activity correlation of flavonoids for inhibition of bovine lens
aldose reductase.

Iinuma M, Tanaka T, Mizuno M, Katsuzaki T, Ogawa H.

To clarify the structure-activity correlation of flavonoids for inhibition of
aldose reductase, about fifty flavonoid compounds were screened. The presence of
hydrophobic substituents on the A ring and hydrophilic substituents on the B
ring of the flavonoid skeleton was suggested to improve the potency of
inhibitory activity. The activities of extracts of Scutellaria baicalensis,
Andrographis paniculata and Gutierrezia microcephala are also described.

PMID: 2509087 [PubMed - indexed for MEDLINE]

129: Bangladesh Med Res Counc Bull. 1989 Jun;15(1):34-7.

Antifertility effect of andrographis paniculata in mice.

Zoha MS, Hussain AH, Choudhury SA.

Antifertility effect of Andrographis Paniculata (AP) was observed in mice under
different experimental conditions. When sun-dried powder of AP was mixed with
animal's food (Rats Pelletts) in a dose of 2G per Kg. B.W. per day and was
allowed to consume by the female mice daily for a period of six weeks, none of
the animal (100%) were pregnant when mated with the male of proven fertility who
did not receive the drug. On the other hand, the majority of the control female
mice (95.2%) who did not receive the drug were pregnant when mated with the
similar type of male as in the experimental group, and they continued to give
birth to litters of usual size and number (average 5-6) for subsequent six
matings.

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

PMID: 2818412 [PubMed - indexed for MEDLINE]

130: Zhong Yao Tong Bao. 1987 Jun;12(6):15-8.

[Cultivation of Andrographis paniculata]

[Article in Chinese]

Zhou Z.

PMID: 3446398 [PubMed - indexed for MEDLINE]

131: Planta Med. 1987 Apr;53(2):135-40.

In vivo and in vitro effects of kalmegh (Andrographis paniculata) extract and
andrographolide on hepatic microsomal drug metabolizing enzymes.

Choudhury BR, Haque SJ, Poddar MK.

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

PMID: 3602136 [PubMed - indexed for MEDLINE]

132: Methods Find Exp Clin Pharmacol. 1985 Dec;7(12):617-21.

Andrographolide and kalmegh (Andrographis paniculata) extract: effect on
intestinal brush-border membrane-bound hydrolases.

Choudhury BR, Poddar MK.

Oral (p.o.) administration of a single dose of kalmegh leaf extract (KE; 0.5
g/kg and 1.0 g/kg) or andrographolide (A; 5 mg/kg and 10 mg/kg) to adult male
albino rats (100-120 g) produced a dose-related and time-dependent
characteristic activation of brush-border membrane-bound hydrolases, viz.
lactase, maltase and sucrase in three regions of small intestine (viz. duodenum,
jejunum and ileum). The maximum stimulation of these disaccharidases was
obtained at 6 hr of either KE or A administration. Further, it was also noted
that the extent of activation of the disaccharidases with KE or A, both at
higher and lower doses, followed the order: (a) Maltase greater than sucrase
greater than lactase in duodenum and (b) Maltase greater than lactase greater
than sucrase in jejunum and ileum. Long term administration (for 7, 15 and 30
consecutive days) of either KE (500 p.o.) or A (5 mg/kg/day; p.o.) stimulated
lactase, maltase and sucrase in all parts of the small intestine. Maximum
stimulation of lactase and maltase was noted after 30 consecutive days of
treatment while sucrase exhibited maximum activation after 15 consecutive of
treatment with either KE or A. These results suggest that both KE and A
accelerate intestinal digestion and absorption of carbohydrate by activating
these intestinal disaccharidases.

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

PMID: 3938507 [PubMed - indexed for MEDLINE]

133: Zhong Yao Tong Bao. 1985 Jul;10(7):38-42.

[Pharmacological studies on thirteen kinds of injections from Andrographis
paniculata. I. Antipyretic, anti-inflammatory effects and toxicity]

[Article in Chinese]

Deng WL.

Publication Types:
Comparative Study

PMID: 2932241 [PubMed - indexed for MEDLINE]

134: Methods Find Exp Clin Pharmacol. 1984 Sep;6(9):481-5.

Andrographolide and kalmegh (Andrographis paniculata) extract: in vivo and in
vitro effect on hepatic lipid peroxidation.

Choudhury BR, Poddar MK.

Single or repeated (for 15 consecutive days) oral administration of kalmegh leaf
extract (500 mg/kg) or its bitter principle, andrographolide (5 mg/kg), to adult
male albino rats (b.wt. 125-150 g) produced no significant change in NADPH
induced hepatic microsomal lipid peroxidation. Carbontetrachloride (5 ml/kg)
induced hepatic microsomal lipid peroxidation was decreased when the rats were
pretreated (for 4 hr), but only with a single dose and not with long term
administration of kalmegh or andrographolide. In vitro carbontetrachloride (1
microliter) induced hepatic microsomal lipid peroxidation was completely
normalized by kalmegh leaf extract (0.5 and 5.0 micrograms/mg protein) or
andrographolide (0.5 and 5.0 micrograms/mg protein). At the higher concentration
of carbontetrachloride (2 microliter), hepatic microsomal lipid peroxidation
remained significantly increased (25 %) in the presence of andrographolide (0.5
microgram/mg protein), but not in the presence of kalmegh extract (0.5
microgram/protein). These results suggest that kalmegh leaf extract has more
protective action on carbontetrachloride-induced hepatic toxicity than its
bitter principle, andrographolide.

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

PMID: 6513681 [PubMed - indexed for MEDLINE]

135: J Helminthol. 1982 Jun;56(2):81-4.

Filaricidal properties of a wild herb, Andrographis paniculata.

Dutta A, Sukul NC.

Water decoction of the leaves of Andrographis paniculata killed in vitro the
microfilaria of Dipetalonema reconditum in 40 min. Three subcutaneous injections
of the extract into infected dogs at 0.06 ml per kg body-weight reduced the
number of microfilariae in blood by more than 85%. The larvae were not totally
eliminated with more infections but the reduced microfilarial level persisted.
No toxic effect of the extract was observed in rabbits. The treated dogs became
lethargic initially for a week, probably due to the mass killing of
microfilariae.

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

PMID: 7201486 [PubMed - indexed for MEDLINE]

136: Yao Xue Xue Bao. 1982 Jun;17(6):435-40.

[Isolation and structure of two new diterpenoid glucosides from Andrographis
paniculata Nees]

[Article in Chinese]

Hu CQ, Zhou BN.

Publication Types:
English Abstract

PMID: 7148467 [PubMed - indexed for MEDLINE]

137: Yao Xue Xue Bao. 1980 Dec;15(12):750-60.

[Morphological and histological studies on Andrographis paniculata (Burm. F.)
Nees. and comparison with four other Acanthaceae herbs (author's transl)]

[Article in Chinese]

Chen JH, Jiang RL.

Publication Types:
Comparative Study
English Abstract

PMID: 7257802 [PubMed - indexed for MEDLINE]

138: Indian J Exp Biol. 1978 Jul;16(7):830-2.

Influence of Andrographis paniculata (Kalmegh) on bile flow & hexabarbitone
sleeping in experimental animals.

Chaudhuri SK.

PMID: 700830 [PubMed - indexed for MEDLINE]

139: Indian J Physiol Pharmacol. 1975 Jan-Mar;19(1):UNKNOWN.

Screening of indigenous plants for anthelmintic action against human Ascaris
lumbricoides: Part--II.

Raj RK.

Alcoholic extracts of the rhizomes of Alpinia galanga, Andrographis paniculata,
bark of Cinnamomum zeylanicum, rind of Citrus decumana, Desmodium triflorum,
seeds of Hydnocarpus wightiana, rhizomes of Kaempfaria galanga, Lippia
nodiflora, tender leaves of Morinda citrifolia, rhizomes of Pollia serzogonian,
Tephrosia purpuria and rhizomes of Zingiber zerumbeth showed good in vitro
anthelmintic activity against human Ascaris lumbricoides. While, the alcoholic
extracts of the bark of Alibzzia lebbek, the bulb of Allium sativum, rhizomes of
Alpinia calcaratta, rind of Citrus acida, rind of Citrus aromatium, rind of
Citrus medica, rhizomes of Curcuma aromatica and rind of Punica granatum showed
moderate invitro activity.

PMID: 1158424 [PubMed - indexed for MEDLINE]

140: Biochem J. 1974 Dec;144(3):585-92.

Biosynthesis of trans, trans- and cis, trans-farnesols by soluble enzymes from
tissue cultures of Andrographis paniculata.

Overton KH, Roberts FM.

PMID: 4468823 [PubMed - indexed for MEDLINE]

141: Ind Med Gaz. 1951 Mar;86(3):96-7.

Andrographolide, the active constituent of Andrographis paniculata Nees; a
preliminary communication.

CHAKRAVARTI RN, CHAKRAVARTI D.

PMID: 14860885 [PubMed - OLDMEDLINE]

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