Clinical Studies

Abstracts are presented below for clinical studies on Phyllanthus Amarus.

  • Botanical Name: Phyllanthus Amarus

  • Ayurvedic Name: Bhumyamlaki

  • Common Name: Phyllanthus Amarus

Phyllanthus Amarus

Plant Phytonutrient Profile


1: Phytochem Anal. 2006 Nov;17(6):394-7.

Quantitative determination of phyllanthin and hypophyllanthin in Phyllanthus
species by high-performance thin layer chromatography.

Tripathi AK, Verma RK, Gupta AK, Gupta MM, Khanuja SP.

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

A simple, precise and rapid high-performance thin-layer chromatographic method
has been developed for the estimation of phyllanthin (1) and hypophyllanthin
(2), the important lignans of Phyllanthus species, especially Phyllanthus
amarus. Separation of 1 and 2 was carried out on silica gel 60 F254 layers
eluted with hexane:acetone:ethyl acetate (74:12:8), and the analytes were
visualised through colour development with vanillin in concentrated sulphuric
acid and ethanol. Scanning and quantification of spots was performed at 580 nm.
Recoveries of 1 and 2 were 98.7 and 97.3%, respectively. The method was
validated and the peak purities and limits of detection and quantification were
determined.

PMID: 17144246 [PubMed - in process]

2: Planta Med. 2006 Dec;72(15):1353-8. Epub 2006 Oct 20.

The cytotoxic effect and the multidrug resistance reversing action of lignans
from Phyllanthus amarus.

Leite DF, Kassuya CA, Mazzuco TL, Silvestre A, de Melo LV, Rehder VL, Rumjanek
VM, Calixto JB.

Instituto de Bioquimica Medica, Universidade Federal do Rio de Janeiro, UFRJ,
Rio de Janeiro, RJ, Brazil.

Multidrug resistance (MDR) constitutes the major obstacle to the successful
treatment of cancer. In several cancer cells, MDR is thought to be mediated by
the super-expression of P-glycoprotein (Pgp). Pgp extrudes drugs from the cells,
therefore reducing their cytotoxicity, and its activity inhibition may reverse
the MDR phenotype. The present study evaluated the possible cytotoxic effect and
MDR reversing properties of the extract and compounds isolated from Phyllanthus
amarus. To this purpose, two human leukaemia cell lines were employed: K-562 and
its vincristine-resistant counterpart Lucena-1, a Pgp-overexpressing subline. We
report here that Lucena-1 was significantly more resistant to the cytotoxicity
of P. amarus derivatives: the hexane extract (HE, 100 microg/mL), the
lignans-rich fraction (LRF, 100 microg/mL) and the lignans nirtetralin (NIRT,
43.2 microg/mL), niranthin (NIRA, 43 microg/mL) or phyllanthin (PHYLLA, 43
microg/mL) exerted cytotoxic effects on K-562 cells with 40.3, 66.0, 62.0, 61.0
or 24.1% of cell death, respectively. The cellular toxicity observed on Lucena-1
was 16.3, 40.4, 29.4, 30.2, or 24.8%, respectively. However, cell treatment with
the lignan phyltetralin (PHYLT) up to 41.6 microg/mL had no cytotoxic action on
either of the cell lines. P. amarus derivatives were also found to be effective
in inhibiting Pgp activity as assessed by rhodamine accumulation in Lucena-1
cells, as were the classical Pgp inhibitors, cyclosporine A (160 nM), PSC-833 (2
microM) and verapamil (5 microM). The lignan NIRT produced the most potent
inhibition (EC (50) = 29.4 microg/mL) followed by NIRA (44.3 microg/mL), LRF
(49.1 microg/mL), PHYLT (99.4 microg/mL), PHYLLA and HE (> 100 microg/mL).
Lucena-1 cells were more resistant to daunorubicin-induced cell death (LC (50) =
50 microM) than K562 cells (LC (50) = 4.95 microM). Of note, the P. amarus
derivatives significantly potentiated 5 microM daunorubicin-induced cell death
in Lucena-1 cells (P < 0.01) but not in K562 cells. After treatment only with P.
amarus derivatives (100 microg/mL HE, 30 microg/mL LRF, 12.9 microg/mL NIRA,
43.2 microg/mL NIRT, 43 microg/mL PHYLLA or 41.6 microg/mL PHYLT), the Lucena-1
cellular viability was 83.7, 85.3, 101, 69.7, 75.6 or 88.7%, respectively,
whereas the in the presence of daunorubincin, which was not cytotoxic PER SE,
the cell viability decreased to 42.9, 42.2, 64.2, 35.4, 30.4 or 52.6%,
respectively. Together, these results suggest a potential action of P. amarus
derivatives as MDR reversing agents, mainly due to their ability to synergize
with the action of conventional chemotherapeutics.

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

PMID: 17054045 [PubMed - in process]

3: Planta Med. 2006 Dec;72(15):e359-e361. Epub 2006 Oct 20.

Supporting Information to "The Cytotoxic Effect and the Multidrug Resistance
Reversing Action of Lignans from Phyllanthus amarus"

Leite DF, Kassuya CA, Mazzuco TL, Silvestre A, de Melo LV, Rehder VL, Rumjanek
VM, Calixto JB.

Instituto de Bioquimica Medica, Universidade Federal do Rio de Janeiro, UFRJ,
Rio de Janeiro, RJ, Brazil.

PMID: 17054044 [PubMed - as supplied by publisher]

4: Eur J Pharmacol. 2006 Sep 28;546(1-3):182-8. Epub 2006 Jul 22.

Antiinflammatory and antiallodynic actions of the lignan niranthin isolated from
Phyllanthus amarus. Evidence for interaction with platelet activating factor
receptor.

Kassuya CA, Silvestre A, Menezes-de-Lima O Jr, Marotta DM, Rehder VL, Calixto
JB.

Department of Pharmacology, Center of Biological Sciences, Universidade Federal
de Santa Catarina, UFSC, Florianopolis, SC, Brazil.

Previous studies have shown that the extracts obtained from Phyllanthus amarus,
and some of the lignans isolated from it, exhibit pronounced antiinflammatory
properties. In the present study, we have assessed whether the antiinflammatory
actions of these lignans can be mediated by interaction with platelet activating
factor (PAF) receptor or interference with the action of this lipid. The local
administration of nirtetralin, phyltetralin or niranthin (30 nmol/paw), similar
to WEB2170 (a PAF receptor antagonist, 30 nmol/paw), significantly inhibited
PAF-induced paw oedema formation in mice. The extracts of P. amarus (100
microg/ml) and niranthin (30 microM), but not nirtetralin or phyltetralin (30
microM), decreased the specific binding of [(3)H]-PAF in mouse cerebral cortex
membranes. Furthermore, both niranthin and WEB2170 displaced, in a
concentration-dependent manner, the [(3)H]-PAF binding sites. The mean IC(50)
values from these effects were 6.5 microM and 0.3 microM, respectively.
Additionally, both niranthin and WEB2170 (30 nmol/paw) inhibited the increase of
myeloperoxidase activity induced by PAF injection in the mouse paw. When
assessed the mouse model of pleurisy induced by PAF, pretreatment with niranthin
(100 micromol/kg, p.o.) or WEB2170 (1.7 micromol/kg, i.p.) significantly
inhibited PAF-induced protein extravasations. Moreover, in the rat model of
PAF-induced allodynia, both niranthin (30 nmol/paw) and WEB2170 (30 nmol/paw)
treatment significantly inhibited PAF-induced allodynia. In addition, niranthin
had a rapid onset and long-lasting antiallodynic action when compared with
WEB2170. Collectively, the present findings suggest that niranthin exhibits
antiinflammatory and antiallodynic actions which are probably mediated through
its direct antagonistic action on the PAF receptor binding sites.

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

PMID: 16925995 [PubMed - indexed for MEDLINE]

5: Fitoterapia. 2006 Dec;77(7-8):511-4. Epub 2006 Jul 15.

Hypoglycemic and hypocholesterolemic activities of the aqueous leaf and seed
extract of Phyllanthus amarus in mice.

Adeneye AA, Amole OO, Adeneye AK.

Department of Pharmacology, Lagos State University College of Medicine, P.M.B.
21266, Ikeja, Lagos, Nigeria. [email protected]

The effect of the aqueous leaf and seed extracts of Phyllanthus amarus at oral
dose of 150, 300 and 600 mg/kg was investigated for their antidiabetic and
anti-lipidemic potentials. The extract produced a dose-dependent decrease in the
fasting plasma glucose and cholesterol, and reduction in weights in treated
mice. The results suggest that the extract could be enhancing peripheral
utilization of glucose but the mechanisms on how this works remain unclear.

PMID: 16905277 [PubMed - indexed for MEDLINE]

6: Asian Pac J Cancer Prev. 2006 Apr-Jun;7(2):299-302.

Inhibition of N-Methyl N'-nitro-N-nitrosoguanidine (MNNG) induced gastric
carcinogenesis by Phyllanthus amarus extract.

Raphael KR, Sabu M, Kumar KH, Kuttan R.

Amala Cancer Research Centre, Thrissur, Kerala 680 555, India.

Chemopreventive activity of Phyllanthus amarus Schum & Thonn (Euphorbiaceae)
extract was studied with regard to N-methyl N'-nitro-N-nitrosoguanidine (MNNG)
induced stomach cancer in Wistar rats. Administration of the extract with MNNG
significantly reduced the incidence of gastric neoplasms in rats (44%) as well
as their numbers. Moreover, elevated levels of enzymes in the stomach were found
to be reduced by P. amarus administration. For example, gamma-glutamyl
transpeptidase activity was decreased from 20.3 +/- 6.7 mmol/min/mg protein to
almost normal levels (2.8 +/- 0.9) by 750 mg/kg body weight of the extract.
Similarly glutathione S-transferase activity (1317.6 +/- 211 n mol/min/mg
protein) and glutathione reductase (368 +/- 66) levels in the MNNG treated group
were found to be lowered to 494.8 +/- 76 and 192 +/- 45, respectively, while
reduced glutathione (GSH) was increased from 4.6+/- 0.9 to 8.5+/-1.4 n
mol/min/mg protein. AgNOR dots and clusters, indicators of cellular
proliferation, which were increased by MNNG treatment, became near to normal in
P. amarus treated animals.

PMID: 16839226 [PubMed - indexed for MEDLINE]

7: Biol Pharm Bull. 2006 Jul;29(7):1310-3.

Inhibition of drug metabolizing enzymes (cytochrome P450) in vitro as well as in
vivo by Phyllanthus amarus SCHUM & THONN.

Hari Kumar KB, Kuttan R.

Amala Cancer Research Centre, Thrissur, India.

An alcoholic extract of Phyllanthus amarus (P. amarus) was found to inhibit
cytochrome P450 (P450) enzymes both in vivo as well as in vitro. This was
studied using specific resorufin derivatives, as substrate for isoenzymes in the
P450 super family. Concentration needed for 50% inhibition of
7-ethoxyresorufin-O-deethylase (EROD), CYP1A1 was 4.6 microg/ml while
concentration needed for 7-methoxyresorufin-O-demethylase (MROD) CYP1A2 was
7.725 microg/ml and 7-pentoxyresorufin-O-depentylase (PROD), CYP2B1/2 was found
to be 4.18 microg/ml indicating that the extract inhibited the P450 enzymes at
very low concentration. Extract also inhibited the activity of aniline
hydroxylase (an indicator of CYP 2E1 activity, IC(50) 50 microg/ml) and
aminopyrine demethylase (an indicator of CYP 1A, 2A 2B, 2D and 3A activity,
IC(50) >1000 microg/ml). Oral administration of the extract was also found to
reduce the elevated P450 enzyme activities produced by phenobarbitone by 50% at
250 mg/kg body weight. The implication of these results on the inhibition of
carcinogenesis produced by the extract is discussed.

PMID: 16819159 [PubMed - indexed for MEDLINE]

8: J AOAC Int. 2006 May-Jun;89(3):619-23.

High-performance thin-layer chromatography densitometric method for simultaneous
quantitation of phyllanthin, hypophyllanthin, gallic acid, and ellagic acid in
Phyllanthus amarus.

Dhalwal K, Biradar YS, Rajani M.

B.V. Patel Pharmaceutical Education and Research Development (PERD) Centre,
Thaltej-Gandhinagar Hwy, Thaltej, Ahmedabad 380 054, Gujarat, India.

Whole plant of Phyllanthus amarus Linn. is a reputed drug of the Indian systems
of medicine that is used as hepatoprotective agent. A simple high-performance
thin-layer chromatography (HPTLC) densitometric method has been developed for
the simultaneous quantitation of phyllanthin, hypophyllanthin, gallic acid, and
ellagic acid in the whole plant of P. amarus. They were found at levels of 0.37,
1.16, 0.36, and 0.17% (w/w), respectively. The method was validated for
precision, repeatability, and accuracy. Instrumental precision was found to be
0.54, 0.93, 0.08, and 0.78% (coefficient of variation, CV); repeatability of the
method was 1.01, 0.79, 0.98, and 1.06% (CV) for phyllanthin, hypophyllanthin,
gallic acid, and ellagic acid, respectively. Accuracy of the method was
determined by a recovery study conducted at 3 different levels, and the average
recovery was found to be 99.09% for phyllanthin, 99.27% for hypophyllanthin,
98.69% for gallic acid, and 100.49% for ellagic acid. The proposed HPTLC method
was found to be simple, precise, specific, sensitive, and accurate and can be
used for routine quality control of raw material of P. amarus and formulations
containing P. amarus. It also has the applicability in quantitating any of these
marker compounds in other drugs.

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

PMID: 16792060 [PubMed - indexed for MEDLINE]

9: J Ethnopharmacol. 2006 Oct 11;107(3):449-55. Epub 2006 Apr 18.

alpha-Amylase inhibitory activity of some Malaysian plants used to treat
diabetes; with particular reference to Phyllanthus amarus.

Ali H, Houghton PJ, Soumyanath A.

Pharmacognosy Research Laboratories, Pharmaceutical Sciences Research Division,
King's College London, Franklin-Wilkins Building, 150, Stamford Street, London
SE1 9NN, United Kingdom.

Extracts of six selected Malaysian plants with a reputation of usefulness in
treating diabetes were examined for alpha-amylase inhibition using an in vitro
model. Inhibitory activity studied by two different protocols (with and without
pre-incubation) showed that Phyllanthus amarus hexane extract had alpha-amylase
inhibitory properties. Hexane and dichloromethane extracts of Anacardium
occidentale, Lagerstroemia speciosa, Averrhoa bilimbiPithecellobium jiringa and
Parkia speciosa were not active when tested without pre-incubation. Extraction
and fractionation of Phyllanthus amarus hexane extract led to the isolation of
dotriacontanyl docosanoate, triacontanol and a mixture of oleanolic acid and
ursolic acid. Dotriacontanyl docosanoate and the mixture of oleanolic acid and
ursolic acid are reported from this plant species for the first time. All
compounds were tested in the alpha-amylase inhibition assay and the results
revealed that the oleanolic acid and ursolic acid (2:1) mixture was a potent
alpha-amylase inhibitor with IC(50)=2.01 microg/ml (4.41 microM) and that it
contributes significantly to the alpha-amylase inhibition activity of the
extract. Three pure pentacyclic triterpenoids, oleanolic acid, ursolic acid and
lupeol were shown to inhibit alpha-amylase.

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

PMID: 16678367 [PubMed - indexed for MEDLINE]

10: Nat Prod Res. 2006 Apr;20(4):323-6.

Antimicrobial potentiality of Phyllanthus amarus against drug resistant
pathogens.

Mazumder A, Mahato A, Mazumder R.

Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra,
Ranchi - 835 215, India. [email protected]

The antimicrobial potentiality of the methanolic extract of Phyllanthus amarus
(Family: Euphorbiaceae) was studied against some drug resistant pathogenic
bacterial strains by disc diffusion and agar dilution method. The extract showed
significant concentration-dependent antibacterial activity particularly against
gram-negative microbes. The study illustrated the claim of the usefulness of the
plant in dysenteric and diarrheal infections and also suggested its use in
fever. The antibacterial action was mainly due to the isolated phyllanthin.

PMID: 16644526 [PubMed - indexed for MEDLINE]

11: Phytother Res. 2005 Nov;19(11):971-6.

Some clinico-pathological changes associated with the aqueous extract of the
leaves of Phyllanthus amarus in rats.

Adedapo AA, Adegbayibi AY, Emikpe BO.

Department of Veterinary Physiology and Pharmacology, University of Ibadan,
Nigeria. [email protected]

The pathological changes of the aqueous crude extract of the leaves of
Phyllanthus amarus were studied in 32 male rats over a period of 30 days. The
animals were divided into four groups of eight animals per group. The aqueous
crude extract was prepared and administered orally using a cannula to rats in
three groups receiving doses of 400 mg/kg, 800 mg/kg and 1,000 mg/kg but the
fourth group served as a control and received distilled water only. Blood
samples were collected for haematological and serum biochemical analysis. Organs
such as the liver, kidney, testes and pancreas were also assessed for
histopathological changes. The study showed that the extract caused a decrease
in the red blood cell (RBC) count, packed cell volume (PCV), haemoglobin
concentration (Hb), but an increase in the white blood cell (WBC) count. The
extract also resulted in an increase in the levels of aspartate amino
transferase (AST), total and conjugated bilirubin, total protein and albumin.
The study, however, caused a decrease in the level of alanine amino transferase
(ALT). Histopathologically, there were cases of protein casts in the kidney
tubules with tubular nephrosis, foci of lymphocytic infiltration at the portal
areas of the liver as well as marked testicular degeneration with severe
disorganization of seminiferous tubules, which were devoid of spermatic cells. A
reduction in the weight of the experimental animals was also noted in this
study. It thus shows that Phyllanthus amarus has potential toxic properties.

PMID: 16317655 [PubMed - indexed for MEDLINE]

12: J Ethnopharmacol. 2006 Mar 8;104(1-2):79-86. Epub 2005 Oct 19.

Comparative pharmacognostic studies of three Phyllanthus species.

Khatoon S, Rai V, Rawat AK, Mehrotra S.

Pharmacognosy and Ethnopharmacology Division, National Botanical Research
Institute, Lucknow 226001, India. [email protected]

Different species of Phyllanthus are considered to be very effective
hepatoprotective agents in the Indian indigenous systems of medicine and are
considered bitter, astringent, stomachic, diuretic, febrifuge, deobstruant and
antiseptic. Still ayurvedic practitioners prescribed fresh juice of 'Bhuiamlki'
for jaundice. Various species of Phyllanthus are being sold in India under the
trade name 'Bhuiamlki'. During market surveillance of herbal drug, it was
observed that almost all the commercial samples, either comprise of Phyllanthus
amarus Schum & Thonn. or Phyllanthus maderaspatensis Linn. or mixture of
Phyllanthus amarus, Phyllanthus fraternus Webster. and Phyllanthus
maderaspatensis. Therefore, in this context the detailed pharmacognostical
evaluation of all the three species has been carried out with the aim to
establish the identification markers of this important hepatoprotective agent
(effective in hepatitis B too). The study conclude that all the three species
can be differentiated on the basis of macro and microscopic characters,
physico-chemical values, HPTLC fingerprint profile, and detection of phyllanthin
and hypophyllanthin as marker components. Besides, an interesting conclusion can
also be drawn that phyllanthin and hypophyllanthin said to protect hepatocytes
against carbon tetrachloride and galactosamine induced toxicity, may not be
exclusively responsible for hepatoprotective activity as these are present only
in Phyllanthus amarus while Phyllanthus fraternus and Phyllanthus
maderaspatensis also possess significant hepatoprotective activity.

Publication Types:
Comparative Study

PMID: 16236476 [PubMed - indexed for MEDLINE]

13: Phytother Res. 2005 Sep;19(9):812-5.

Toxic effects of chromatographic fractions of Phyllanthus amarus on the serum
biochemistry of rats.

Adedapo AA, Abatan MO, Idowu SO, Olorunsogo OO.

Department of Veterinary Physiology/Pharmacology, University of Ibadan, Nigeria.
[email protected]

Chromatographic fractions obtained from Phyllanthus amarus were tested for
toxicity on the serum biochemistry of rats. The results revealed that some
fractions of P. amarus had potentially deleterious effects on the blood and
therefore caution should be exercised in the use of P. amarus as a medicinal
plant. Copyright 2005 John Wiley & Sons, Ltd.

PMID: 16220579 [PubMed - indexed for MEDLINE]

14: Bioorg Med Chem. 2005 Dec 1;13(23):6470-6. Epub 2005 Sep 6.

Tannins and related compounds induce nitric oxide synthase and cytokines gene
expressions in Leishmania major-infected macrophage-like RAW 264.7 cells.

Kolodziej H, Burmeister A, Trun W, Radtke OA, Kiderlen AF, Ito H, Hatano T,
Yoshida T, Foo LY.

Institute of Pharmacy, Pharmaceutical Biology, Freie Universitat Berlin,
Germany. [email protected]

Some polyphenol-containing extracts (Pelargonium sidoides, Phyllanthus amarus)
and representatives of simple phenols (shikimic acid 3- and 5-O-gallate),
flavan-3-ols (epigallocatechin 3-gallate), proanthocyanidins (a hexamer) and
hydrolysable tannins (corilagin, casuariin, geraniin) were studied for gene
expressions (iNOS, IL-1, IL-10, IL-12, IL-18, TNF-alpha, IFN-alpha/gamma) by
RT-PCR. All extracts and compounds were capable of enhancing the iNOS and
cytokine mRNA levels in parasitised cells when compared with those in
non-infected conditions.

PMID: 16143535 [PubMed - indexed for MEDLINE]

15: Planta Med. 2005 Aug;71(8):721-6.

Anti-inflammatory properties of extracts, fractions and lignans isolated from
Phyllanthus amarus.

Kassuya CA, Leite DF, de Melo LV, Rehder VL, Calixto JB.

Department of Pharmacology, Center of Biological Sciences, Universidade Federal
de Santa Catarina (UFSC), Florianopolis, SC, Brazil.

This study assessed the anti-inflammatory effect of the extracts and purified
lignans obtained from Phyllanthus amarus. Given orally, the hexane extract (HE),
the lignan-rich fraction (LRF), or the lignans phyltetralin, nirtetralin,
niranthin, but not hypophyllanthin or phyllanthin, inhibited carrageenan
(Cg)-induced paw oedema and neutrophil influx. The HE, the LRF or nirtetralin
also inhibited the increase of IL1-beta tissue levels induced by Cg.
Furthermore, bradykinin (BK)-, platelet activating factor (PAF)- and
endothelin-1 (ET-1)-induced paw oedema were significantly inhibited by the HE or
LRF while histamine- and substance P-induced paw oedema were unaffected.
Finally, nirtetralin or phyltetralin caused inhibition of paw oedema induced by
PAF or ET-1. These results show that the HE, the LRF and the lignans niranthin,
phyltetralin and nirtetralin exhibited marked anti-inflammatory properties and
suggest that these lignans seem to be the main active principles responsible for
the anti-inflammatory properties reported for the HE of P. amarus.

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

PMID: 16142635 [PubMed - indexed for MEDLINE]

16: Phytomedicine. 2005 Jun;12(6-7):494-500.

Chemoprotective activity of an extract of Phyllanthus amarus against
cyclophosphamide induced toxicity in mice.

Kumar KB, Kuttan R.

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

The effect of 75% methanolic extract of the plant Phyllanthus amarus (P. amarus)
was studied against cyclophosphamide (CTX) induced toxicity in mice.
Administration of CTX (25 mg/kg b.wt, i.p.) for 14 days produced significant
myelosuppression as seen from the decreased WBC count and bone marrow
cellularity. Administration of P. amarus extract at doses 250 and 750 mg/kg b.wt
significantly reduced the myelosuppression and improved the WBC count, bone
marrow cellularity as well as the number of maturing monocytes. CTX treatment
also reduced the activity of glutathione system and increased the activity of
phase I enzyme that metabolize CTX to its toxic side products. P. amarus
administration was found to decrease the activity of phase I enzyme.
Administration of P. amarus also increased the cellular glutathione (GSH) and
glutathione-S-transferase (GST), thereby decreasing the effect of toxic
metabolites of CTX on the cells. Administration of P. amarus did not reduce the
tumor reducing activity of CTX. In fact, there was a synergistic action of CTX
and P. amarus in reducing the solid tumors in mice. Results indicated that
administration of P. amarus can significantly reduce the toxic side effects of
CTX and is not interfering with the antitumor efficiency of CTX.

PMID: 16008127 [PubMed - indexed for MEDLINE]

17: Chemosphere. 2005 Dec;61(11):1644-50. Epub 2005 Jun 29.

Effect of cadmium on growth, ultramorphology of leaf and secondary metabolites
of Phyllanthus amarus Schum. and Thonn.

Rai V, Khatoon S, Bisht SS, Mehrotra S.

Pharmacognosy and Ethnopharmacology Division, National Botanical Research
Institute, Rana Pratap Marg, Lucknow 226001, Uttar Pradesh, India.
[email protected]diffmail.com

The pollution is increasing in the environment by different kinds of human
activities, which results in the accumulation of heavy metals including cadmium
in the soil and water and it causes different types of problems to living
beings. As the plants are utilized by human being as food and medicine,
therefore, it is mandatory to see the effect of metals on plants. In this
context, efforts have been made to observe the effect of different concentration
of Cadmium (Cd) on Phyllanthus amarus Schum. and Thonn., because Cd is the
widespread metal and the plants response to low and high level of exposure is a
complex phenomenon. P. amarus is mostly grown as weed in agricultural and waste
lands. It is a reputed plant used in Indian indigenous systems of medicine with
hepatoprotective, diuretic, stomachic properties and is recently being used for
the treatment of hepatitis B. The study revealed that Cd causes significant
decrease in fresh and dry weight, length of root and shoot, protein,
chlorophyll, carotenoids and sugar and increase in starch content. It is
interesting to note that the therapeutically active compounds-phyllanthin and
hypophyllanthin, enhanced at certain levels of Cd due to abiotic stress.
Besides, the ultramorpholical changes were also observed in stomatal opening and
wax deposition on both the surfaces of leaves.

PMID: 15992855 [PubMed - indexed for MEDLINE]

18: J Ethnopharmacol. 2005 Jun 3;99(2):309-12. Epub 2005 Apr 8.

Antibacterial screening of some Peruvian medicinal plants used in Calleria
District.

Kloucek P, Polesny Z, Svobodova B, Vlkova E, Kokoska L.

Department of Crop Sciences and Agroforestry, Institute of Tropics and
Subtropics, Czech University of Agriculture Prague, Kamycka 129, 165 21 Prague
6-Suchdol, Czech Republic.

Nine ethanol extracts of Brunfelsia grandiflora (Solanaceae), Caesalpinia
spinosa (Caesalpiniaceae), Dracontium loretense (Araceae), Equisetum giganteum
(Equisetaceae), Maytenus macrocarpa (Celastraceae), Phyllanthus amarus
(Euphorbiaceae), Piper aduncum (Piperaceae), Terminalia catappa (Combretaceae),
and Uncaria tomentosa (Rubiaceae), medicinal plants traditionally used in
Calleria District for treating conditions likely to be associated with
microorganisms, were screened for antimicrobial activity against nine bacterial
strains using the broth microdilution method. Among the plants tested,
Phyllanthus amarus and Terminalia catappa showed the most promising
antibacterial properties, inhibiting all of the strains tested with minimum
inhibitory concentrations (MICs) ranging from 0.25 to 16 mg/ml. The extract from
aerial part of Piper aduncum was significantly more active against Gram-positive
(MICs ranging from 1 to 2 mg/ml) than against Gram-negative bacteria (MICs > 16
mg/ml).

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

PMID: 15894143 [PubMed - indexed for MEDLINE]

19: Biomed Environ Sci. 2004 Sep;17(3):359-65.

Evaluation of inhibitory effect of the plant Phyllanthus amarus against
dermatophytic fungi Microsporum gypseum.

Agrawal A, Srivastava S, Srivastava JN, Srivasava MM.

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

OBJECTIVE: The antifungal activity of various solvent extracts (such as ether,
chloroform, ethyl acetate and ethyl alcohol) of the plant Phyllanthus amarus
against dermatophytic fungi Microsporum gypseum was observed. METHOD: Antifungal
bioassay in terms of reduction in weight, colony diameter and sporulation of the
target fungal colony was carried out using Broth Dilution method. Results Root
part of the plant, extracted in various organic solvents did not show any
noticeable antifungal activity. The percentage inhibition observed in different
solvent extracts of aerial part was found as reduction in weight: chloroform
[50.3%], ethyl acetate [27.7%] and ethyl alcohol [12.1%], reduction in colony
diameter: chloroform [53.4%], ethyl acetate [31.4%] and ethyl alcohol [15.0%]
and reduction in sporulation: maximum inhibition in chloroform extract, at test
concentration of 4000 ppm at incubation period of 8 days. CONCLUSION: Chloroform
fraction of the aerial part of the plant P. amarus shows significant inhibitory
effect against dermatophytic fungi M. gypseum and requires chemical
characterization for its bioactive principle.

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

PMID: 15602834 [PubMed - indexed for MEDLINE]

20: Afr J Med Med Sci. 2004 Jun;33(2):115-9.

Efficacy of herbal remedies used by herbalists in Oyo State Nigeria for
treatment of Plasmodium falciparum infections--a survey and an observation.

Ajaiyeoba EO, Falade CO, Fawole OI, Akinboye DO, Gbotosho GO, Bolaji OM, Ashidi
JS, Abiodun OO, Osowole OS, Itiola OA, Oladepo O, Sowunmi A, Oduola AM.

Department of Pharmacognosy, University of Ibadan, Ibadan, Nigeria.

In the course of evaluating the contribution of phytomedicine to possible drug
discovery of antimalarial drugs, an ethnomedical survey of specialized children
traditional clinics was done. In the observational multi center study, efficacy
of eight different herbal remedies, each consisting of 3-8 ingredients and
administered by herbalists were investigated in clients enrolled in the six
traditional clinics in Oyo (urban center) and Otu (rural center) of Oyo State,
Nigeria. The clients, aged between six months and fifteen years with clinical
symptoms of malaria were enrolled in the clinics of the herbalists, as their
usual practice. Oral informed consents were obtained from their parents or
guardians. Microscopic diagnosis of malaria infection was used to evaluate
parasitaemia and validate efficacy of herbal remedies. Results of the analysis
showed that, of the 163 clients of the herbalists, only 62 (30 from Oyo, 32 from
Otu) had microscopically confirmed P. falciparum infection. Only results from 54
clients (29/30 (Oyo) and 25/32 (Otu) with P. falciparum infection could be
evaluated. Plasmodium falciparum infection in 88% (23/29) of clients from Oyo
responded to treatment with the herbal remedies while cure rate in clients from
Otu was 42% (13/25). Parasite densities ranged from 171 to 53,613
parasites/microl blood and 87 to 36,209 parasites/microl blood in patients from
Oyo and Otu respectively. The herbalists administered the remedies and Gossypium
arboreum, Anarcadium occidentalis, Citrus medica, Phyllanthus amarus and Lippia
multiflora were the main ingredients in the efficacious remedies. The herbalists
gave detailed descriptions of each of the 8 herbal remedies proffered. The
results confirm the efficacy of two of the eight herbal remedies, thereby
validating the role of ethnomedicine as a possible source for the discovery of
new chemotherapeutic agents in the treatment of P. falciparum malaria.

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

PMID: 15565927 [PubMed - indexed for MEDLINE]

21: Clin Gastroenterol Hepatol. 2004 Nov;2(11):947-56.

Use of herbal supplements for chronic liver disease.

Levy C, Seeff LD, Lindor KD.

Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Minnesota
55905, USA.

BACKGROUND & AIMS: Complementary and alternative medicine (CAM) is becoming
popular among patients with liver disease. Although there is a growing body of
evidence regarding potential mechanisms of action of these and other herbs,
caution must be used to interpret the results of the few clinical trials
available. Our goal was to discuss the biologic rationale for the use of
specific herbs (silymarin, glycyrrhizin, sho-saiko-to, Phyllanthus amarus ,
Picrorrhiza kurroa , Compound 861, CH-100, and LIV.52) in the treatment of
chronic liver diseases, as well as the evidence for their efficacy and adverse
effects according to clinical trials. METHODS: Because of the relative paucity
of clinical studies using herbs, every trial published in English was reviewed.
RESULTS: Although many trials suggest that these herbs can decrease serum
transaminase levels, the effects on hepatic histopathology and long-term
survival are either poorly studied or conflicting. LIV.52 has been withdrawn
from the market because of deleterious effects in patients with liver disease.
CONCLUSIONS: Based on current evidence, we cannot recommend the use of herbal
supplements for the routine treatment of any chronic liver disease and further
well-designed clinical trials are necessary.

Publication Types:
Review

PMID: 15551246 [PubMed - indexed for MEDLINE]

22: Antiviral Res. 2004 Nov;64(2):93-102.

Concerted inhibitory activities of Phyllanthus amarus on HIV replication in
vitro and ex vivo.

Notka F, Meier G, Wagner R.

Institute of Medical Microbiology and Hygiene, University of Regensburg,
Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany.
[email protected]

Phyllanthus amarus derived preparations were previously shown to inhibit RT
inhibitor-resistant HIV variants as efficiently as wild-type strains. The drugs
target different steps of the HIV life cycle, thereby presenting multiple
antiviral activities. Here we show that a water/alcohol extract blocks HIV-1
attachment and the HIV-1 enzymes integrase, reverse transcriptase and protease
to different degrees. A gallotannin containing fraction and the isolated
ellagitannins geraniin and corilagin were shown to be the most potent mediators
of these antiviral activities. The P. amarus derived preparations blocked the
interaction of HIV-1 gp120 with its primary cellular receptor CD4 at 50%
inhibitory concentrations of 2.65 (water/alcohol extract) to 0.48 microg/ml
(geraniin). Inhibition was also evident for the HIV-1 enzymes integrase
(0.48-0.16 microg/ml), reverse transcriptase (8.17-2.53 microg/ml) and protease
(21.80-6.28 microg/ml). In order to prove the in vivo relevance of these
biological activities, plant material was administered orally to volunteers and
a potent anti-HIV activity in blood could be demonstrated. Sera at a final
concentration of 5% reduced HIV replication by more than 30%. These results
support the conclusion that P. amarus has inhibitory effects on HIV not only in
vitro but also in vivo.

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

PMID: 15498604 [PubMed - indexed for MEDLINE]

23: J Environ Biol. 2003 Oct;24(4):391-4.

Insecticidal activity of the plant Phyllanthus amarus against Tribolium
castaneum.

Khanna S, Srivastava CN, Srivastava MM, Srivastava S.

Department of Chemistry, Dayalbagh Educational Institute, Dayalbagh, Agra-282
005, Uttar Pradesh, India.

The plant Phyllanthus amarus is used as folk medicine since the year 1800 and
has been established for its important medicinal properties particularly for
liver ailments. The present communication explores the insecticidal activity of
ethanolic extract of aerial and root parts of this plant against stored grain
pest Tribolium castaneum. LC 50 values of ethanolic aerial part were 895.77,
473.91, 279.89 and 260.85 microg/cm2, while 512.62, 376.96, 248.88 and 209.79
microg/cm2 for ethanolic root part at the exposure of 3, 5, 7, 9 and 11 days
respectively. Ethanolic root extract possessed significant insecticidal activity
against T. castaneum.

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

PMID: 15248651 [PubMed - indexed for MEDLINE]

24: J Radiat Res (Tokyo). 2004 Mar;45(1):133-9.

Protective effect of an extract of Phyllanthus amarus against radiation-induced
damage in mice.

Kumar KB, Kuttan R.

Amala Cancer Research Centre.

The radioprotective effect of an extract of the plant Phyllanthus amarus (P.
amarus) was investigated in adult BALB/c mice. P. amarus extract (750 mg/kg b.wt
and 250 mg/kg b.wt) was administered orally to mice for five days prior to whole
body radiation (6 Gy) and for one month after radiation. The animals were
sacrificed on days 3, 9, 12, and 30 after radiation. P. amarus significantly
increased the total W.B.C count, bone marrow cellularity, and alpha-esterase
activity as compared to untreated radiation-exposed animals. P. amarus treatment
also increased the activity of various antioxidant enzymes, such as superoxide
dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione
peroxidase (GPX), and glutathione reductase (GR), both in blood and tissue,
which were reduced by radiation treatment. There was also a significant increase
in the glutathione (GSH) levels of blood and tissue. Lipid peroxidation levels,
which were increased after radiation, were significantly reduced by P. amarus
treatment, both in serum and liver. The results collectively indicate that P.
amarus extract could increase the antioxidant defense mechanism in mice and
there by protect the animals from radiation-induced cellular damage.

Publication Types:
Comparative Study

PMID: 15133301 [PubMed - indexed for MEDLINE]

25: J Vet Sci. 2003 Aug;4(2):181-5.

Morphometric and histopathological studies on the effects of some
chromatographic fractions of Phyllanthus amarus and Euphorbia hirta on the male
reproductive organs of rats.

Adedapo AA, Abatan MO, Akinloye AK, Idowu SO, Olorunsogo OO.

Departments of Veterinary Physiology and Pharmacology.University of Ibadan,
Ibadan, Nigeria.

The aqueous crude extracts of P. amarus and E. hirta were administered to thirty
eight-week old sexually mature male albino to determine the effects of these
extracts on the male reproductive organs of these animals. The results from this
study revealed that the aqueous crude extracts of P. amarus and E. hirta caused
varying degrees of testicular degeneration as well as reduction in the mean
seminiferous tubular diameter (STD) in the treated rats. It thus shows that the
aqueous crude extracts of P. amarus and E. hirta have potentially deleterious
effects on the testes and accessory organs of rats. Great caution should
therefore be exercised in the use of these plants for medicinal purpose.

PMID: 14610373 [PubMed - indexed for MEDLINE]

26: Eur J Pharmacol. 2003 Oct 8;478(2-3):145-53.

Anti-allodynic and anti-oedematogenic properties of the extract and lignans from
Phyllanthus amarus in models of persistent inflammatory and neuropathic pain.

Kassuya CA, Silvestre AA, Rehder VL, Calixto JB.

Department of Pharmacology, Center of Biological Sciences, Universidade Federal
de Santa Catarina, Rua Ferreira Lima, 82, 88015-420 Florianopolis, SC, Brazil.

This study investigated the anti-allodynic and anti-oedematogenic effects of the
hexanic extract, lignan-rich fraction and purified lignans from a plant used in
the traditional medicine, Phyllanthus amarus, in the inflammatory and
neuropathic models of nociception. The hexanic extract inhibited the allodynia
and the oedema induced by the intraplantar injection of complete Freund's
adjuvant (CFA). The inhibition observed was 76 +/- 7% (ipsilateral paw), 64 +/-
7% (contralateral paw), and 41 +/- 2% (oedema). Otherwise, the lignan-rich
fraction or the pure lignans did not affect CFA-induced allodynia. Administered
chronically, the lignan fraction reduced CFA-induced paw oedema (39 +/- 9%).
When evaluated in the model of neuropathic pain caused by partial ligation of
sciatic nerve, the hexanic extract inhibited the mechanical allodynia (77 +/-
7%), with a similar efficacy to the gabapentin (71 +/- 10%). The anti-allodynic
effects of hexanic extract of P. amarus seem not to be associated with the
impairment of motor co-ordination or with the development of tolerance. Finally,
the treatment with hexanic extract inhibited the increase of myeloperoxidase
activity, either following intraplantar injection of CFA or after sciatic nerve
injury. It is concluded that, apart from its anti-inflammatory actions, which
are probably linked to the presence of lignans, another as yet unidentified
active principle(s) present in the hexanic extract of P. amarus produces
pronounced anti-allodynia in two models of inflammatory and neuropathic pain.
Considering that few drugs are currently available for the treatment of chronic
pain, especially of the neuropathic type, the present results may have clinical
relevance and open new possibilities for the development of new anti-allodynic
drugs.

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

PMID: 14575799 [PubMed - indexed for MEDLINE]

27: J Ethnopharmacol. 2003 Aug;87(2-3):193-7.

Inhibition of experimental gastric lesion and inflammation by Phyllanthus amarus
extract.

Raphael KR, Kuttan R.

Amala Cancer Research Centre, Thrissur, Kerala 680 553, India.

Methanolic extract of Phyllanthus amarus Shum & Thonn (Euphorbiaceae) 50, 200,
and 1000 mg/kg body weight significantly inhibited gastric lesions, induced by
intragastric administration of absolute ethanol (8 ml/kg). Mortality, increased
stomach weight, ulcer index, and intraluminal bleeding were reduced
significantly by Phyllanthus amarus. Biochemical analysis indicated that reduced
glutathione (GSH) of gastric mucosa produced by ethanol administration was
significantly elevated by treatment with Phyllanthus amarus extract. Aqueous and
methanol extracts of Phyllanthus amarus produced an inhibition of rat paw edema
up to 42% compared to control in 3h and continued up to 8h. Anti-oxidant
activity of the extract as well as presence of tannins in the extract may be
responsible for these observed activities.

PMID: 12860307 [PubMed - indexed for MEDLINE]

28: 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]

29: Antiviral Res. 2003 Apr;58(2):175-86.

Inhibition of wild-type human immunodeficiency virus and reverse transcriptase
inhibitor-resistant variants by Phyllanthus amarus.

Notka F, Meier GR, Wagner R.

CMI-Centers for Medical Innovation AG, Fraunhofer Str 15, 82152 Martinsried,
Germany. [email protected]

Substantial progress has been made in research on natural products which
effectively inhibit HIV-1 replication. Many active compounds were isolated from
traditionally used medicinal plants including Phyllanthus species. This study
shows that aqueous as well as alcohol-based Phyllanthus amarus extracts potently
inhibit HIV-1 replication in HeLa CD4(+) cells with 50% effective concentration
(EC(50)) values ranging from 0.9 to 7.6 microg/ml. A gallotannin enriched
fraction showed enhanced activity (0.4 microg/ml), and the purified gallotannins
geraniin and corilagin were most active (0.24 microg/ml). HIV-1 replication was
also blocked in CD4(+) lymphoid cells with comparable EC(50) values. Applying a
cell-based internalization assay, we could demonstrate 70-75% inhibition of
virus uptake at concentrations of 2.5 microg/ml for the water/alcohol extract
and geraniin. In addition, a concentration-dependent inhibition of HIV-1 reverse
transcriptase (RT) could be demonstrated in vitro. The 50% inhibitory
concentration (IC(50)) values varied from 1.8 to 14.6 microg/ml. The ability to
inhibit replication of a variety of RT inhibitor-resistant HIV-1 strains points
to the potential of P. amarus extracts, as natural products, in the chemotherapy
of HIV infections.

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

PMID: 12742578 [PubMed - indexed for MEDLINE]

30: Indian J Exp Biol. 2002 Aug;40(8):905-9.

Hypoglycemic effect of methanol extract of Phyllanthus amarus Schum & Thonn on
alloxan induced diabetes mellitus in rats and its relation with antioxidant
potential.

Raphael KR, Sabu MC, Kuttan R.

Amala Cancer Research Center, Amalanagar, Thrissur 680 553, India.

Methanolic extract of P. amarus was found to have potential anti-oxidant
activity as it could inhibit lipid peroxidation, and scavenge hydroxyl and
superoxide radicals in vitro. The amount required for 50% inhibition of lipid
peroxide formation was 104 microg/ml and the concentrations needed to scavenge
hydroxyl and superoxide radicals were 117 and 19 microg/ml respectively. The
extract was found to reduce the blood sugar in alloxan diabetic rats at 4th hr
by 6% at a dose level of 200 mg/kg body wt and 18.7% at a concentration of 1000
mg/kg body wt. Continued administration of the extract for 15 days produced
significant (P < 0.001) reduction in blood sugar. On 18th day after alloxan
administration values were almost similar to normal in the group taking 1000
mg/kg body wt.

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

PMID: 12597020 [PubMed - indexed for MEDLINE]

31: J Hepatol. 2003 Mar;38(3):289-97.

Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX-2,
and cytokines via the NF-kappaB pathway.

Kiemer AK, Hartung T, Huber C, Vollmar AM.

Department of Pharmacy, Center of Drug Research, University of Munich,
Butenandtstr. 5-13, 81377 Munich, Germany. [email protected]

BACKGROUND/AIMS: Phyllanthus amarus is a herbal medicine traditionally applied
in the treatment of viral hepatitis. Aim of this study was to investigate
potential anti-inflammatory properties of standardized P. amarus extracts
concerning a potential influence of P. amarus on endotoxin-induced nitric oxide
synthase (iNOS), cyclooxygenase (COX-2), and cytokine production in vivo and in
vitro. METHODS: Investigations were performed in rat Kupffer cells (KC), in
RAW264.7 macrophages, in human whole blood, and in mice. Cells were stimulated
with lipopolysaccharides (LPS) in the presence or absence of P. amarus extracts
(hexane, EtOH/H(2)O), mice were treated with galactosamine/LPS as a model for
acute toxic hepatitis. Nitrite was measured by Griess assay, prostaglandin E(2)
(PGE(2)) by radioimmunoassay, and cytokines by enzyme-linked immunosorbent
assay. iNOS and COX-2 were determined by Western blot, activation of NF-kappaB
and AP-1 by EMSA. RESULTS: P. amarus EtOH/H(2)O and hexane extracts showed an
inhibition of LPS-induced production of NO and PGE(2) in KC and in RAW264.7. The
extracts also attenuated the LPS-induced secretion of tumor necrosis factor
(TNF-alpha) in RAW264.7 as well as in human whole blood. Both extracts reduced
expression of iNOS and COX-2 and inhibited activation of NF-kappaB, but not of
AP-1. P. amarus inhibited induction of interleukin (IL)-1beta, IL-10, and
interferon-gamma in human whole blood and reduced TNF-alpha production in vivo.
CONCLUSIONS: This work shows that standardized extracts of P. amarus inhibit the
induction of iNOS, COX-2, and TNF-alpha. Therefore, we report for the first time
an anti-inflammatory potential of this traditionally employed herbal medicine
both in vitro and in vivo.

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

PMID: 12586294 [PubMed - indexed for MEDLINE]

32: J Gastroenterol Hepatol. 2002 Dec;17 Suppl 3:S370-S376.

Herbal medicines for liver diseases in India.

Thyagarajan S, Jayaram S, Gopalakrishnan V, Hari R, Jeyakumar P, Sripathi M.

The use of natural remedies for the treatment of liver diseases has a long
history, starting with the Ayurvedhic treatment, and extending to the Chinese,
European and other systems of traditional medicines. The 21st century has seen a
paradigm shift towards therapeutic evaluation of herbal products in liver
diseases by carefully synergizing the strengths of the traditional systems of
medicine with that of the modern concept of evidence-based medicinal evaluation,
standardization of herbal products and randomized placebo controlled clinical
trials to support clinical efficacy. The present review provides the status
report on the scientific approaches made to herbal preparations used in Indian
systems of medicine for the treatment of liver diseases. In spite of the
availability of more than 300 preparations for the treatment of jaundice and
chronic liver diseases in Indian systems of medicine using more than 87 Indian
medicinal plants, only four terrestrial plants have been scientifically
elucidated while adhering to the internationally acceptable scientific
protocols. In-depth studies have proved Sylibum marianum to be anti-oxidative,
antilipidperoxidative, antifibrotic, anti-inflammatory, immunomodulating and
liver regenerative. Glycyrrhiza glabra has been shown to be hepatoprotective and
capable of inducing an indigenous interferon. Picrorhiza kurroa is proved to be
anti-inflammatory, hepatoprotective and immunomodulatory. Extensive studies on
Phyllanthus amarus have confirmed this plant preparation as being anti-viral
against hepatitis B and C viruses, hepatoprotective and immunomodulating, as
well as possessing anti-inflammatory properties. For the first time in the
Indian systems of medicine, a chemo-biological fingerprinting methodology for
standardization of P. amarus preparation has been patented. Copyright 2002
Blackwell Publishing Asia Pty Ltd

PMID: 12472966 [PubMed - as supplied by publisher]

33: Teratog Carcinog Mutagen. 2002;22(4):285-91.

Anti-mutagenic activity of Phyllanthus amarus Schum & Thonn in vitro as well as
in vivo.

Raphael KR, Ajith TA, Joseph S, Kuttan R.

Amala Cancer Research Centre, Thrissur, Kerala, India.

Methanolic extract of Phyllanthus amarus was tested for its anti-mutagenic
activity in Salmonella typhimurium strains TA1535, TA100, and TA102 (Ames test).
P. amarus extract was able to inhibit the activation and mutagenicity of
2-acetaminofluorene (2-AAF) and aflatoxinB(1) at concentrations of 0.25-2
mg/plate. It was also found to inhibit mutagenicity induced by direct acting
mutagens sodium azide (NaN(3)), N-methyl-N-nitro-N-nitrosoguanidine (MNNG), and
4-nitro-0-phenylenediamine (NPD), at concentrations of 1 mg to 0.25 mg/plate.
Urinary mutagenicity produced in rats by benzo[a] pyrene was found to be
significantly inhibited by the oral administration of Phyllanthus extract. These
results indicate significant anti-mutagenicity of the extract in vitro as well
as in vivo. Copyright 2002 Wiley-Liss, Inc.

Publication Types:
In Vitro

PMID: 12111712 [PubMed - indexed for MEDLINE]

34: J Ethnopharmacol. 2002 Jun;81(1):17-22.

Antitumour and anticarcinogenic activity of Phyllanthus amarus extract.

Rajeshkumar NV, Joy KL, Kuttan G, Ramsewak RS, Nair MG, Kuttan R.

Amala Cancer Research Centre, Thrissur, Kerala, 680-553, India.

Aqueous extract of Phyllanthus amarus (P. amarus) treatment exhibited potent
anticarcinogenic activity against 20-methylcholanthrene (20-MC) induced sarcoma
development and increased the survival of tumour harboring mice. The extract
administration (p.o) was also found to prolong the life span of Dalton's
Lymphoma Ascites (DLA) and Ehrlich Ascites Carcinoma (EAC) bearing mice and
reduced the volume of transplanted solid tumours. The extract inhibited aniline
hydroxylase, a P-450 enzyme. The concentration required for 50% inhibition
(IC(50)) was found to be 540 microg/ml. The extract was found to inhibit DNA
topoisomerase II of Saccharomyces cerevisiae mutant cell cultures and inhibited
cell cycle regulatory enzyme cdc25 tyrosine phosphatase (IC(50-25) microg/ml).
Antitumour and anticancer activity of P. amarus may be related with the
inhibition of metabolic activation of carcinogen as well as the inhibition of
cell cycle regulators and DNA repair.

PMID: 12020923 [PubMed - indexed for MEDLINE]

35: Phytomedicine. 2002 Jan;9(1):26-32.

Antimutagenic and anticarcinogenic effects of Phyllanthus amarus.

Sripanidkulchai B, Tattawasart U, Laupatarakasem P, Vinitketkumneun U,
Sripanidkulchai K, Furihata C, Matsushima T.

Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon
Kaen University, Thailand. [email protected]

This study aimed to examine the antimutagenic and anticarcinogenic potential of
Phyllanthus amarus Schum. et Thonn. using the bacterial preincubation mutation
assay and an in-vivo alkaline elution method for DNA single-strand breaks in
hamster liver cells. The aqueous extract of the entire plant showed an
antimutagenic effect against induction by 2-aminofluorene (AF2),
2-aminoanthracene (2AA) and 4-nitroquinolone-1-oxide (4-NQO) in Salmonella
typhimurium strains TA98 and TA100, and in Escherichia coli WP2 uvrA/pKM101. All
the results were dose-dependent; however, inhibition of
N-ethyl-N-nitrosoguanidine (ENNG)-induced mutagenesis was observed only with S.
typhimurium TA100. The extract also exhibited activity against 2-nitrofluorene
(2NF) and sodium azide-induced mutagenesis with S. typhimurium TA98 and TA100,
respectively. Based on the alkaline elution method, the plant extract prevented
in vivo DNA single-strand breaks caused by dimethylnitrosamine (DMN) in hamster
liver cells. When the extract was administered 30 min prior to the
administration of DMN, the elution rate constant decreased more than 2.5 times,
compared to that of control. These results indicate that P. amarus possesses
antimutagenic and antigenotoxic properties.

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

PMID: 11924760 [PubMed - indexed for MEDLINE]

36: Indian J Exp Biol. 2001 Nov;39(11):1184-7.

High frequency in vitro propagation of Phyllanthus amarus Schum. & Thom. by
shoot tip culture.

Bhattacharyya R, Bhattacharya S.

Department of Botany, Bose Institute, Calcutta, India.

With the aim of micropropagation of Phyllanthus amarus, an important medicinal
herb, shoot tips were cultured in Murashige and Skoog's medium supplemented with
kinetin/ BAP singly or in combination with IAA. Growth regulators at lower range
(0.1-1.0 mg L(-1)) stimulated direct regeneration of shoots. Kinetin was
superior to BAP and kinetin-IAA combination was more suitable than kinetin
alone. About 15 shoots were yielded per explant after 30 days of culture in the
medium containing kinetin and IAA both at 0.1mg L(-1). The cluster of
proliferated shoots elongated and rooted simultaneously under the same treatment
following another subculture, thus shortening the total time schedule of
micropropagation. Shoot tips of regenerated shoots were continuously used to
regenerate new shoots with periodic transfer to fresh medium resulting in a
steady supply of normal, healthy plants without any deviation in the production
rate during a continuous one year culture. Micropropagated plants were
successfully established in soil with high survivality (80%).

PMID: 11906118 [PubMed - indexed for MEDLINE]

37: Phytother Res. 2001 Nov;15(7):577-80.

The effect of Phyllanthus amarus aqueous extract on blood glucose in non-insulin
dependent diabetic patients.

Moshi MJ, Lutale JJ, Rimoy GH, Abbas ZG, Josiah RM, Swai AB.

Institute of Traditional Medicine, MUCHS, Box 65001, Dar es Salaam, Tanzania.
[email protected]

The glycaemic response to 124.5 +/- 9.3 (mean +/- SD) g of pancakes was
monitored in 21 non-insulin dependent diabetic (NIDDM) patients while on oral
hypoglycaemics, after a 1-week washout period and after a 1-week twice daily
treatment with 100 mL of an aqueous extract from 12.5 g of powdered aerial parts
of Phyllanthus amarus. After the 1-week washout period, the fasting blood
glucose (FBG) and postprandial blood glucose increased significantly compared
with treatment on oral hypoglycaemics ( p < 0.05). After a 1-week herbal
treatment no hypoglycaemic activity was observed. Both FBG and postprandial
blood glucose remained very similar to that recorded after the washout period (
p > 0.05). Both liver and renal functions based on alanine transaminase (ALAT)
and serum creatinine, respectively, were not significantly affected by the use
of the extract. Although the lymphocyte and monocyte levels were significantly
decreased ( p < 0.05) and the granulocyte level was significantly increased
after treatment ( p < 0.05) the overall total white blood cell (WBC) count and
haemoglobin (Hb) were not significantly affected by the 1 week herbal treatment.
We conclude that 1 week treatment with the aqueous extract of Phyllanthus amarus
was incapable of lowering both FBG and postprandial blood glucose in untreated
NIDDM patients. Copyright 2001 John Wiley & Sons, Ltd.

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

PMID: 11746836 [PubMed - indexed for MEDLINE]

38: Southeast Asian J Trop Med Public Health. 2001 Mar;32(1):140-2.

A comparative study of Phyllanthus amarus compound and interferon in the
treatment of chronic viral hepatitis B.

Xin-Hua W, Chang-Qing L, Xing-Bo G, Lin-Chun F.

Tropical Medicine Institute, Guangzhou University of Traditional Chinese
Medicine, Guangdong, People's Republic of China.

Fifty-five patients with chronic viral hepatitis B were randomly divided into
two groups. Thirty patients were treated with Phyllanthus amarus compound (PA
Co) for three months in the treatment group, another 25 patients were treated
with domestic recombinant human interferon alpha-1b (IFN-alpha 1b) for three
months as controls. The total effective rate in the treatment group was 83.3%,
showing no significant difference from the control (p>0.05). The normalization
rates of ALT, A/G and SB in the treatment group were 73.3%, 80.0% and 78.2%
respectively, which were significantly higher than that in the control (p<0.05).
The negative conversion rates of HBeAg and HBV-DNA in the treatment group were
42.3% and 47.8%, showing no significant difference from the control (p>0.005).
It is indicated that PA Co has remarkable effect for chronic viral hepatitis B
in recovery of liver function and inhibition of the replication of HBV.

Publication Types:
Clinical Trial
Comparative Study
Randomized Controlled Trial

PMID: 11485076 [PubMed - indexed for MEDLINE]

39: Liver. 2001 Aug;21(4):280-6.

Chinese medicinal herbs for chronic hepatitis B: a systematic review.

Liu J, McIntosh H, Lin H.

The Cochrane Hepato-Biliary Group, The Copenhagen Trial Unit, Centre for
Clinical Intervention Research, Copenhagen University Hospital, H:S
Rigshospitalet, Copenhagen, Denmark. [email protected]

AIMS/BACKGROUND: Chronic hepatitis B is a serious health problem worldwide.
Chinese medicinal herbs are widely used for treatment of chronic hepatitis B in
China and many clinical trials have been conducted. This systematic review is to
assess the efficacy and safety of Chinese medicinal herbs for chronic hepatitis
B. METHODS: Randomised clinical trials comparing Chinese medicinal herbs versus
placebo, no intervention, nonspecific treatment, or interferon treatment for
chronic hepatitis B with > or = 3 months follow-up were included. No language
and blinding limitations were applied. The electronic databases were searched,
combined with handsearches on Chinese literature. Data were extracted
independently by two reviewers. The methodological quality of trials was
assessed by the Jadad-scale plus allocation concealment. RESULTS: Nine
randomised trials (n=936) were included, with only one being of high quality.
There was a funnel plot asymmetry (intercept 3.37, p=0.047). Compared to
nonspecific treatment or placebo, the herbal compound Fuzheng Jiedu Tang showed
an effect on clearance of serum HBsAg (relative risk 5.19, 95% CI 1.24-21.79),
HBeAg (10.85, 3.56-33.06), and HBV DNA (8.50, 1.23-58.85). Polyporus umbellatus
polysaccharide showed an effect on serum HBeAg (3.06, 1.13-8.29) and HBV DNA
(4.14, 1.0-17.19); Phyllanthus amarus showed an effect on serum HBeAg (3.35,
1.49-7.56). Phyllanthus compound and kurorinone showed no significant difference
on clearance of serum HBeAg and HBV DNA and on alanine aminotransferase
normalisation compared to interferon. No serious adverse event was observed.
CONCLUSIONS: Chinese medicinal herbs are not recommended for chronic hepatitis B
because of the publication bias and low quality of the trials. Rigorously
designed, randomised, double-blind, placebo-controlled trials are needed.

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

PMID: 11454192 [PubMed - indexed for MEDLINE]

40: Cochrane Database Syst Rev. 2001;(2):CD002231.

Chinese medicinal herbs for asymptomatic carriers of hepatitis B virus
infection.

Liu JP, McIntosh H, Lin H.

The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical
Intervention Research, Copenhagen University Hospital, Dept. 7701, H:S
Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark, DK-2100.
[email protected]

BACKGROUND: About 350 million people are chronically infected carriers of
hepatitis B virus and are at a higher risk of serious illness and death from
cirrhosis of the liver and liver cancer. Chinese medicinal herbs have been used
widely for more than 2000 years to treat chronic liver disease. OBJECTIVES: To
assess whether Chinese medicinal herbs are effective and safe for treating
asymptomatic carriers of hepatitis B virus. SEARCH STRATEGY: The trials
registers of the Cochrane Hepato-Biliary Group, the Cochrane Library and the
Cochrane Complementary Medicine Field were searched in combination with MEDLINE,
EMBASE, and handsearches of Chinese journals and conference proceedings.
SELECTION CRITERIA: Randomised or quasi-randomised trials (minimum follow-up
three months) in asymptomatic carriers of hepatitis B virus. Chinese medicinal
herbs (single herb or compound of herbs) compared with placebo, no intervention,
general non-specific treatment, or interferon treatment. Trials of Chinese
medicinal herbs plus interferon versus interferon alone were also included. DATA
COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers.
Analysis was performed by intention-to-treat where possible. Pre-specified
subgroup analyses were: ethnic origin, age at time of infection, and single herb
or compound of herbs. MAIN RESULTS: Three randomised clinical trials (307
patients) that followed patients for three months or more after the end of
treatment were included. The methodological quality was poor. The herbal
compound 'Jianpi Wenshen recipe' had significant effects on viral markers
compared to interferon: relative risk 2.40 (95% CI 1.01 to 5.72) for clearance
of serum HBsAg, 2.03 (95% CI 0.98 to 4.20) for clearance of HBeAg, and 2.54 (95%
CI 1.13 to 5.70) for seroconversion of HBeAg to anti-HBe. Phyllanthus amarus and
Astragalus membranaceus showed no significant antiviral effect compared with
placebo. Analysis of pooling eight randomised clinical trials with less than
three months follow-up did not show a significant benefit of Chinese medicinal
herbs on viral markers. Data on long-term clinical outcomes and quality of life
were lacking. REVIEWER'S CONCLUSIONS: Based on one low quality trial, the
medicinal herb 'Jianpi Wenshen recipe' may have an antiviral activity in
asymptomatic carriers of hepatitis B virus. However, rigorous randomised,
double-blind, placebo-controlled trials are needed before herbs should be used
for this condition.

Publication Types:
Review

PMID: 11406038 [PubMed - indexed for MEDLINE]

41: Afr J Med Med Sci. 2000 Jun;29(2):119-22.

Anti-diarrhoeal and gastro-intestinal potentials of the aqueous extract of
Phyllanthus amarus (Euphorbiaceae).

Odetola AA, Akojenu SM.

Biochemistry Department, University of Ibadan, Ibadan, Nigeria.

The anti-diarrhoeal and gastro-intestinal protective potentials of aqueous
extract of leaves of Phyllanthus amarus were investigated in mice. Graded doses
of the aqueous extract (100-800 mg/kg) administered orally produced a
dose-related inhibition of gut meal travel distance in normal mice. The highest
intestinal transit inhibition of 31.65% was obtained with 400 mg/kg. In castor
oil induced diarrhoea in mice, P. amarus extract (400 mg/kg) delayed the onset
of diarrhoea, reduced frequency of defecation and reduced gut meal travel
distance significantly resulting in intestinal transit inhibition of 79.94%
compared to 86.92% produced by morphine (100 mg/kg). In addition, the activities
of some intestinal mucosa enzymes (maltase, sucrase, lactase and alkaline
phosphatase) in mice pretreated with extract before castor oil were not as
severely depressed as those in the control (castor oil treated mice).
Phytochemical screening revealed the presence of many secondary metabolites. The
results are discussed with a view to establishing the basis of the use of this
plant in traditional medicine for treatment of diarrhoea and other
gastrointestinal disorders.

PMID: 11379441 [PubMed - indexed for MEDLINE]

42: Phytother Res. 2001 May;15(3):265-7.

Contraceptive effects of Phyllanthus amarus in female mice.

Rao MV, Alice KM.

Reproductive Endocrinology and Toxicology Division, Zoology Department, School
of Sciences, Gujarat University, Ahmedabad - 380009, India.
[email protected]

Antifertility effects of an alcohol extract of the whole plant, Phyllanthus
amarus at a dose of 100 mg/kg body weight for 30 days orally was investigated in
cyclic adult female mice. The results revealed no -significant change in
absolute body and organ weights in extract-fed animals, indicating no alteration
in general metabolic status. Further, feeding had no effect on haematological
and clinical biochemical tests reflecting its non-toxicity. Similarly, uterine
and ovarian biochemical tests showed no change except in 3beta and 17beta
hydroxy steroid dehydrgenase (HSDs) levels, probably affecting hormonal
conversions in the latter. Cohabited females with normal male mice were unable
to become pregnant as their cyclicity was affected. These factors are related to
a change in the hormonal milieu that governs female reproductive function. Upon
withdrawal of feeding for 45 days, these effects were reversible. Thus this
extract manifests a definite contraceptive effect in female mice. Copyright 2001
John Wiley & Sons, Ltd.

Publication Types:
Comparative Study

PMID: 11351367 [PubMed - indexed for MEDLINE]

43: Cochrane Database Syst Rev. 2001;(1):CD001940.

Chinese medicinal herbs for chronic hepatitis B.

Liu JP, McIntosh H, Lin H.

Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical
Intervention Research, Copenhagen University Hospital, Dept. 7701, H:S
Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark, DK-2100. Jianping
[email protected]

BACKGROUND: Hepatitis B virus infection is a serious health problem worldwide.
Traditional Chinese medicinal herbs have been widely used to treat chronic liver
diseases, and many controlled trials have been done to investigate their
efficacy. OBJECTIVES: To assess the efficacy and safety of traditional Chinese
medicinal herbs for chronic hepatitis B infection. SEARCH STRATEGY: Searches
were applied to the following electronic databases: the CHBG Trials Register,
the Cochrane Complementary Medicine Field Trials Register, the Cochrane Library,
MEDLINE, EMBASE and BIOSIS. Five Chinese journals and conference proceedings
were handsearched. No language restriction was used. SELECTION CRITERIA:
Randomised or quasi-randomised trials with at least three months follow-up.
Trials of Chinese medicinal herbs (single or compound) compared with placebo, no
intervention, general non-specific treatment or interferon treatment were
included. Trials of Chinese medicinal herbs plus interferon versus interferon
alone were also included. Trials could be double-blind, single-blind or not
blinded. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two
reviewers. The methodological quality of trials was evaluated using the
Jadad-scale plus allocation concealment. Intention-to-treat analyses were
performed. MAIN RESULTS: Nine randomised trials, including 936 patients, met the
inclusion criteria. Methodological quality was considered adequate in only one
trial. There was a significant funnel plot asymmetry (regression
coefficient=3.37, standard error 1.40, P=0.047). Ten different medicinal herbs
were tested in the nine trials. Compared to non-specific treatment or placebo,
Fuzheng Jiedu Tang (compound of herbs) showed significantly positive effects on
clearance of serum HBsAg, HBeAg, and HBV DNA; Polyporus umbellatus
polysaccharide on serum HBeAg and HBV DNA; Phyllanthus amarus on serum HBeAg.
Phyllanthus compound and kurorinone showed no significant effect on clearance of
serum HBeAg and HBV DNA and on alanine aminotransferase normalisation compared
to interferon treatment. There were no significant effects of the other examined
herbs. REVIEWER'S CONCLUSIONS: Some Chinese medicinal herbs may work in chronic
hepatitis B. However, the evidence is too weak to recommend any single herb.
Rigorously designed, randomised, double-blind, placebo-controlled trials are
required.

Publication Types:
Review

PMID: 11279742 [PubMed - indexed for MEDLINE]

44: J Ethnopharmacol. 2000 Nov;73(1-2):215-9.

Phyllanthus amarus extract administration increases the life span of rats with
hepatocellular carcinoma.

Rajeshkumar NV, Kuttan R.

Amala Cancer Research Centre, Thrissur, 680 553, Kerala, India.

The effect of Phyllanthus amarus extract administration after induction of
hepatocellular carcinoma (HCC) by N-nitrosodiethylamine (NDEA) was studied in
Wistar rats. Administration of an aqueous extract of P. amarus was found to
significantly increase the survival of hepatocellular carcinoma harboring
animals. All the untreated rats died of tumour burden by 33.7+/-1.6 weeks.
Administration of P. amarus extract (150 mg/kg b.w.) after tumour development
increased the survival of animals to an average of 52. 2+/-2.3 weeks. Serum
gamma-glutamyl transpeptidase activity which was elevated to 182+/-23 U/l by
NDEA administration was lowered to 112+/-19 U/l by the administration of P.
amarus extract. Similarly elevated glutathione S-transferase activity
(1534+/-116 nmol/min per mg protein) and glutathione (20.5+/-2.4 nmol/mg
protein) levels in the NDEA administered group were found to be lowered to
1112+/-89 nmol/min per mg protein and 14.2+/-2.2 nmol/mg protein respectively.
P. amarus administration was found to be ineffective in controlling the liver
weight, elevation of tissue gamma-glutamyl transpeptidase, serum alkaline
phosphatase and serum glutamate pyruvate transaminase of HCC harboring animals.

PMID: 11025159 [PubMed - indexed for MEDLINE]

45: J Ethnopharmacol. 2000 Sep;72(1-2):229-38.

Antinociceptive properties of extracts of new species of plants of the genus
Phyllanthus (Euphorbiaceae).

Santos AR, De Campos RO, Miguel OG, Filho VC, Siani AC, Yunes RA, Calixto JB.

Department of Pharmacology (CCB), Centre of Biological Sciences, Universidade
Federal de Santa Catarina, Rua: Ferreira Lima 82, Florianopolis, SC 88015-420,
Brazil.

The hydroalcoholic extract (HE) of the four new species of Phyllanthus, given
intraperitoneally, produced significant inhibition of acetic acid-induced
abdominal constrictions, with mean ID(50) values of 0.3, 1.8, 7.4 and 26.5 mg/kg
for Phyllanthus amarus, Phyllanthus orbiculatus, Phyllanthus fraternus and
Phyllanthus stipulatus, respectively. In the formalin test, the four species of
Phyllanthus, also produced graded inhibition against both phases of
formalin-induced licking, being more active in relation of the late phase. The
HE of the Phyllanthus species elicited significant inhibition of the
capsaicin-induced neurogenic pain, with mean ID(50) values of 8.9, 6.7, >30 and
approximately 30 mg/kg for P. amarus, P. fraternus, P. stipulatus and P.
orbiculatus, respectively. Given orally all HE of the Phyllanthus species were
less potent and efficacious than when given by intraperitoneally. Results of the
present study extend previous data and indicate that all extracts of Phyllanthus
plants so far studied exhibit pronounced antinociception when assessed in
chemical models of nociception, namely acetic acid-induced writhing, and
formalin and capsaicin-induced licking.

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

PMID: 10967476 [PubMed - indexed for MEDLINE]

46: J Gastroenterol Hepatol. 2000 May;15 Suppl:E67-70.

Treatment of chronic liver diseases with traditional Chinese medicine.

Wang BE.

Beijing Friendship Hospital, Capital University of Medical Sciences, PR China.

Traditional Chinese medicine is still being extensively used for treatment of
liver disease in China. The anti-viral herbs, Phyllanthus amarus, P. niruri and
P urninaria, and Oxymatrine extracted from Sophora flavecientis and S.
subprostratae, have been shown to have a remarkable HBV suppressing effect with
a serum conversion rate for HBeAg and HBV DNA around 45%, similar to that of
IFN-alpha. The anti-inflammatory compound, Stronger NeoMinophagen C (SNMC), is a
Japanese preparation of glycerrhizin, extracted from Glyceriza glabra, which has
shown an effective rate of ALT and AST normalization and reduction to < 60 U/L
in 65.6%, and 73.5% of patients. Compound 861, made of 10 herbs with Salvia
miltiorrhiza as its chief component, has been shown experimentally to be
effective in suppressing fibrogenesis, enhancing collagen degradation, and
inhibiting TIMP expression. Clinically, an open trial of 2,000 patients showed
improvement of symptoms in 83% and normalization of serum ALT in 82%. In a
controlled study of 107 patients with HBV-related diseases, double liver
biopsies showed that the fibrosis reversal rate after 6 months treatment with
Cpd 861 was 78% in S2, 82% in S3 (precirrhotic stage) and 75% in S4 (early
cirrhosis), as assessed by Scheuer's and Chevallier's criterion. In conclusion,
traditional Chinese medicine has great potential in the treatment of chronic
hepatitis B.

PMID: 10921385 [PubMed - indexed for MEDLINE]

47: Trop Gastroenterol. 1999 Oct-Dec;20(4):164-6.

A trial of Phyllanthus amarus in acute viral hepatitis.

Narendranathan M, Remla A, Mini PC, Satheesh P.

Department of Gastroenterology, Medical College, Trivandrum, India.

The study was done to know whether the powders of Phyllanthus amarus plants
favourably influence the duration of disease in patients with acute viraus B
hepatitis when compared to placebo. The powders of the plant were given in
capsule form (300 mg capsules--3 capsules--3 capsules thrice daily) and an
antacid powder in similar capsule was used as placebo. Persons with
encephalopathy, preexisting medical conditions or serum bilirubin above 350 iu/l
were excluded from the study. Fifty seven patients were randomized to receive
either the placebo (28 cases) or the drug (28 cases). The two groups were
comparable at the time of entry. Two cases from the placebo and one from the
placebo and one from the drug group dropped out of the study. The duration of
disease (time taken for bilirubin to come to below 2 mg%) was taken as the
outcome measure. The duration of disease in the two groups was compared by Cox's
proportional hazards analysis after adusting for the variables that influence
the duration of jaundice. Only initial serum bilirubin was an independent
predictor of duration of jaundice. The an analysis showed that Phyllanthus
amarus powders did not significantly reduce the duration of jaundice in persons
with virus B hepatitis.

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

PMID: 10769603 [PubMed - indexed for MEDLINE]

48: Cancer Lett. 1999 Feb 8;136(1):11-6.

Effect of Emblica officinalis, Phyllanthus amarus and Picrorrhiza kurroa on
N-nitrosodiethylamine induced hepatocarcinogenesis.

Jeena KJ, Joy KL, Kuttan R.

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

Extracts of Emblica officinalis (EO), Phyllanthus amarus (P. amarus) and
Picrorrhiza kurroa (P. kurroa) significantly inhibited hepatocarcinogenesis
induced by N-nitrosodiethylamine (NDEA) in a dose dependent manner. The
anticarcinogenic activity of these extracts were evaluated by their effect on
tumour incidence, levels of carcinogen metabolizing enzymes, levels of liver
cancer markers and liver injury markers. Animals treated with NDEA alone showed
100% tumour incidence and significantly elevated tissue levels of drug
metabolizing enzymes such as glutathione S-transferase (GST) and aniline
hydroxylase (AH). Treatment of extracts significantly reduced these levels.
Levels of gamma-glutamyl transpeptidase (GGT) were also found to be elevated
both in serum and tissues of tumour bearing animals, while they were
significantly reduced in the treated group. Similar reduction was seen in tissue
levels of reduced glutathione. Serum levels of lipid peroxide (LPO), alkaline
phosphatase (ALP) and glutamate pyruvate transaminase (OPT), which are markers
of liver injury, were also elevated. Morphology of liver tissue and levels of
marker enzymes indicated that these extracts offered protection against chemical
carcinogenesis.

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

PMID: 10211933 [PubMed - indexed for MEDLINE]

49: Eur J Clin Invest. 1997 Nov;27(11):908-15.

Phyllanthus amarus suppresses hepatitis B virus by interrupting interactions
between HBV enhancer I and cellular transcription factors.

Ott M, Thyagarajan SP, Gupta S.

Department of Medicine, Albert Einstein College of Medicine, Bronx 10461, USA.

The Phyllanthus amarus plant suppresses HBV mRNA transcription in vitro and
exhibits therapeutic potential in chronic HBV carriers, although further work is
necessary to define its mechanism of action. Analysis in HuH-7 cells with
transfected plasmids using a luciferase reporter showed that P. amarus
specifically inhibited HBV enhancer I activity. To identify the mechanism of
this HBV enhancer I inhibition, liver-enriched cellular transcription factors
were co-expressed in HuH-7 cells. The C/EBP alpha and beta, as well as HNF-3
alpha and beta transcription factors, significantly up-regulated the HBV
enhancer I activity. In contrast, co-transfection of HNF-I alpha or beta had no
effect upon the HBV enhancer I activity. Exposure to P. amarus inhibited C/EBP
alpha- and beta-mediated up-regulation of HBV enhancer I activity in a
dose-dependent manner, whereas HNF-3 alpha- and beta-mediated up-regulation of
HBV enhancer I was unaffected. In vitro gel shifts showed that P. amarus
inhibited complexing of C/EBP transcription factors to a consensus
oligonucleotide sequence, whereas DNA binding of AP-1 and SP-1 transcription
factors was unaffected. As P. amarus down-regulates HBV mRNA transcription by a
specific mechanism involving interactions between HBV enhancer I and C/EBP
transcription factors, purification and further analysis of the active P. amarus
component will advance insights into its antiviral activity.

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

PMID: 9395786 [PubMed - indexed for MEDLINE]

50: Eur J Clin Invest. 1996 Dec;26(12):1069-76.

Phyllanthus amarus down-regulates hepatitis B virus mRNA transcription and
replication.

Lee CD, Ott M, Thyagarajan SP, Shafritz DA, Burk RD, Gupta S.

Marion Bessin Liver Research Center, Madras, India.

The Phyllanthus amarus plant shows potential for treating hepatitis B virus. To
define the mechanism of action of P. amarus, we used HepG2 2.2.15 cells, which
support hepatitis B virus replication. P. amarus inhibited hepatitis B virus
polymerase activity, decreased episomal hepatitis B virus DNA content and
suppressed virus release into culture medium. To examine transcriptional control
mechanisms, we used G26 hepatitis B virus transgenic mice, which produce serum
HBsAg but neither HBcAg nor virion particles. When P. amarus was administered to
transgenic mice, hepatic HBsAg mRNA levels decreased, indicating transcriptional
or post-transcriptional down-regulation of the transgene. Increase in hepatitis
B virus mRNA expression after stimulation of the glucocorticoid responsive
element was also suppressed by P. amarus, suggesting involvement of the
hepatitis B virus enhancer in this response. Disruption by P. amarus of
hepatitis B virus polymerase activity, mRNA transcription and replication
supports its role as an antiviral agent.

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

PMID: 9013081 [PubMed - indexed for MEDLINE]

51: Indian J Pathol Microbiol. 1996 Jul;39(3):211-5.

Inhibition of HBsAg secretion from Alexander cell line by Phyllanthus amarus.

Jayaram S, Thyagarajan SP.

Department of Microbiology, Dr. ALM Post Graduate Institute of Basic Medical
Sciences, University of Madras, Taramani.

Alexander cell line, an human hepatocellular carcinoma derived cell line which
has the property of secreting HBsAg in the supernatant was used to study the
antiviral property of phyllanthus amarus. Aquous extract of Phyllanthus amarus
was evaluated for its in vitro ability to inhibit HBsAg secretion on a dose
dependent manner. It was seen that P. amarus at 1mg/ml concentration on a single
dose inhibited the secretion of HBsAg for a period of 48 hours. This experiment
proved the anti hepatitis B virus property of P. amarus at cellular level and
further confirmed its beneficial use in the treatment of acute and chronic
hepatitis B and healthy carriers of HBV.

PMID: 8972151 [PubMed - indexed for MEDLINE]

52: Indian J Exp Biol. 1995 Nov;33(11):861-4.

Diuretic, hypotensive and hypoglycaemic effect of Phyllanthus amarus.

Srividya N, Periwal S.

Department of Home Science, Sri Sathya Sai Institute of Higher Learning,
Anantapur, India.

Diuretic, hypotensive and hypoglycaemic effects of Phyllanthus amarus (syn.
Phyllanthus niruri) on human subjects were assessed. Nine mild hypertensives
(four of them also suffering from diabetes mellitus) were treated with a
preparation of the whole plant of P. amarus for 10 days. Suitable parameters
were studied in the blood and urine samples of the subjects, along with
physiological profile and dietary pattern before and after the treatment period.
Significant increase in 24 hr urine volume, urine and serum Na levels was
observed. A significant reduction in systolic blood pressure in non-diabetic
hypertensives and female subjects was noted. Blood glucose was also
significantly reduced in the treated group. Clinical observations revealed no
harmful side effects. These observations indicate that P. amarus is a potential
diuretic, hypotensive and hypoglycaemic drug for humans.

Publication Types:
Clinical Trial
Controlled Clinical Trial

PMID: 8786163 [PubMed - indexed for MEDLINE]

53: J Lab Clin Med. 1995 Oct;126(4):350-2.

Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B:
observations with three preparations from different geographic sites.

Wang M, Cheng H, Li Y, Meng L, Zhao G, Mai K.

Henan Institute of Medical Sciences, Henan Medical University, People's Republic
of China.

It has been suggested that herbs of the Phyllanthus family may have antiviral
activity. We therefore tested the effects of three different Phyllanthus
extracts on the serologic status of 123 patients with chronic hepatitis B.
Eleven patients received an extract of Phyllanthus amarus (L) provided by S.P.
Thyagarajan, Madras, India. Forty-two patients received Phyllanthus niruri (L),
gathered from Hainan Province in China, and 35 patients received an extract of
Phyllanthus urinaria (L), which had been gathered in Henan Province. Thirty-five
control patients received no herbal therapy. The patients receiving Phyllanthus
urinaria (L) were both more likely to lose detectable hepatitis B e-antigen from
their serum and more likely to seroconvert hepatitis B e-antibody status from
negative to positive than were patients given either of the other two
preparations. No patient changed status with respect to hepatitis B s-antigen.

Publication Types:
Clinical Trial
Comparative Study
Controlled Clinical Trial

PMID: 7561442 [PubMed - indexed for MEDLINE]

54: Phytochemistry. 1995 Jan;38(2):307-14.

Inhibition of signal-regulated protein kinases by plant-derived hydrolysable
tannins.

Polya GM, Wang BH, Foo LY.

Department of Biochemistry, La Trobe University, Bundoora, Victoria, Australia.

A variety of hydrolysable tannins purified from Phyllanthus amarus are potent
inhibitors of rat liver cyclic AMP-dependent protein kinase catalytic subunit
(cAK) with IC50 values (concentrations for 50% inhibition) in the range 0.2-1.7
microM. The three most effective compounds of this series of hydrolysable
tannins have five phenolic substituents. These three compounds are also the most
effective inhibitors of wheat embryo Ca(2+)-dependent protein kinase (CDPK), rat
brain Ca(2+)- and phospholipid-dependent protein kinase C (PKC) and
Ca(2+)-calmodulin-dependent myosin light chain kinase (MLCK). The order of
sensitivity for protein kinase inhibition by the hydrolysable tannins studied is
cAK > CDPK > PKC > MLCK. Thus the IC50 values for protein kinase inhibition by
the most potent compound are 0.2 microM (for cAK), 1.8 microM (for CDPK), 26
microM (for PKC) and 56 microM (for MLCK) when protein kinase affinity is
measured using synthetic peptide substrates. These hydrolysable tannin
inhibitors found are the most specific and potent plant-derived inhibitors of
cAK yet found.

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

PMID: 7772301 [PubMed - indexed for MEDLINE]

55: Zhongguo Zhong Yao Za Zhi. 1994 Dec;19(12):750-1, 764.

[Efficacy of Phyllanthus spp. in treating patients with chronic hepatitis B]

[Article in Chinese]

Wang MX, Cheng HW, Li YJ, Meng LM, Mai K.

Henan Institute of Medical Sciences, Zhengzhou.

The efficacy of Phyllanthus amarus produced in india, P. niruri gathered from
hainan province and P. urinaria from henan province was assessed in a total of
88 cases of chronic hepatitis B with 11.42 and 35 each. It was shown that P.
urinaria had the effect of seroconversion on HBeAg from positive to negative as
well as on HBeAb from negative to positive, while the other two herbs had not.
In addition none of these three herbs had similar effect on HBsAg.

Publication Types:
Clinical Trial
Comparative Study
English Abstract
Randomized Controlled Trial

PMID: 7718142 [PubMed - indexed for MEDLINE]

56: Mutat Res. 1994 Sep;322(3):185-92.

In vivo studies of a crude extract of Phyllanthus amarus L. in modifying the
genotoxicity induced in Vicia faba L. by tannery effluents.

Gowrishanker B, Vivekanandan OS.

P.G. & Research Department of Botany, Pachayappa's College, Madras, India.

The genotoxic effects of two types of tannery effluent (Raw-to-Wetblue and
Wetblue-to-Finish) and the antigenotoxic property of a crude extract of
Phyllanthus amarus L. were evaluated using the root meristem of Vicia faba L. as
the in vivo test system. The root tip cells were exposed to the tannery
effluents at different concentrations for varying durations. Squash preparations
were made following Haematoxylin staining procedures. Cytological investigations
revealed a duration- and concentration-dependent decrease in mitotic frequency
and an increase in chromosomal irregularities. The root meristems pre-treated
with effluents for 8 h (Raw-to-Wetblue) and 24 h (Wetblue-to-Finish) which
caused the maximum incidence of mitotic anomalies, were then exposed to the
crude extract of Phyllanthus amarus (0.25, 0.5, 0.75 and 1%) to study its
efficacy modifying genetic damage. It was observed that the root meristems
post-treated with Phyllanthus showed a significant reduction in the frequency of
chromosomal alterations. However, there was no significant variation in the
mitotic frequency. The study suggests that Phyllanthin, a principle of
Phyllanthus amarus, is antigenotoxic.

PMID: 7521518 [PubMed - indexed for MEDLINE]

57: N Z Med J. 1994 Jun 22;107(980):243.

Failure of New Zealand hepatitis B carriers to respond to Phyllanthus amarus.

Milne A, Hopkirk N, Lucas CR, Waldon J, Foo Y.

Hepatitis Foundation, Whakatane.

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

PMID: 8208497 [PubMed - indexed for MEDLINE]

58: Indian J Gastroenterol. 1994 Jan;13(1):7-8.

A two-stage clinical trial of Phyllanthus amarus in hepatitis B carriers:
failure to eradicate the surface antigen.

Doshi JC, Vaidya AB, Antarkar DS, Deolalikar R, Antani DH.

Dr Balabhai Nanavati Hospital and Research Center, Juhu, Bombay.

BACKGROUND: There have been conflicting data in literature about the value of
Phyllanthus amarus in treating hepatitis B virus-related disorders. AIM: To
evaluate the role of Phyllanthus amarus in eradication of the virus in hepatitis
B carriers. METHODS: Phyllanthus amarus was administered to 30 asymptomatic
carriers of hepatitis B surface antigen (HBsAg) in a dosage of 250 to 500 mg
thrice daily for 4 to 8 weeks. RESULTS: None of the 30 subjects cleared HBsAg.
Phyllanthus amarus was well tolerated, with no clinical side effects or changes
in the organ profiles for safety evaluation. CONCLUSION: Phyllanthus amarus is
not effective in clearing HBsAg in asymptomatic carriers of the antigen.

Publication Types:
Clinical Trial

PMID: 8119752 [PubMed - indexed for MEDLINE]

59: J Med Virol. 1993 Dec;41(4):275-81.

Evaluation of anti-hepadnavirus activity of Phyllanthus amarus and Phyllanthus
maderaspatensis in duck hepatitis B virus carrier Pekin ducks.

Munshi A, Mehrotra R, Ramesh R, Panda SK.

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

Extracts of the two traditional Indian herbs, Phyllanthus amarus (P. amarus) and
Phyllanthus maderaspatensis (P. maderaspatensis), described by others as useful
in the treatment of chronic hepatitis B virus infection were studied for
antiviral properties on duck hepatitis B virus infection. One hundred and
fourteen ducks infected posthatch with the duck hepatitis B virus (DHBV) were
divided into groups at three months of age and treated intraperitoneally with
the aqueous, butanol, and alcoholic extracts of these two plants at doses of 25,
50, or 200 mg/kg body weight. Saline-treated animals served as controls. In the
ducks negative for DHBV in serum after treatment, we observed replicative
intermediates in the liver. There was no definite antiviral property observed in
the treated ducks.

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

PMID: 8106861 [PubMed - indexed for MEDLINE]

60: J Med Virol. 1993 May;40(1):53-8.

Evaluation of Phyllanthus amarus and Phyllanthus maderaspatensis as agents for
postexposure prophylaxis in neonatal duck hepatitis B virus infection.

Munshi A, Mehrotra R, Panda SK.

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

The therapeutic potential of plant extracts of Phyllanthus amarus and
Phyllanthus maderas patensis for postexposure prophylaxis against infection by
Hepadnaviruses was studied in ducklings infected by the duck hepatitis B virus
(DHBV). Forty-four Pekin ducklings were inoculated intraperitoneally with DHBV
at 24 hr post-hatch. They were treated by intraperitoneal injection of
Phyllanthus amarus (aqueous extract) (100 mg/kg body weight) or Phyllanthus mad
eraspatensis (alcoholic extract) (100 mg/kg body weight) for a period of 4
weeks. Infected ducklings treated with saline served as controls. Weekly serum
samples obtained before, during, and after treatment were analysed for the
presence of DHBV DNA in serum by dot blot hybridisation using alpha 32P-labelled
probes. Liver tissue was collected after killing the ducks at various time
intervals and was studied for replicative status of the viral DNA and liver
histopathology; 17 of 21 ducks were viraemic on completion of treatment with
Phyllanthus amarus. At 16 week posttreatment follow-up four of seven animals
remained viraemic. Similar results were obtained with Phyllanthus
maderaspatensis. There was no alteration in DHBV replication in the liver. No
toxicity was observed with this treatment. These observations suggest that
Phyllanthus amarus and Phyllanthus maderaspatensis are not useful as therapeutic
agents for postexposure prophylaxis against DHBV infection.

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

PMID: 8515247 [PubMed - indexed for MEDLINE]

61: Antiviral Res. 1993 Mar;20(3):185-92.

Effect of an extract from Phyllanthus amarus on hepatitis B surface antigen gene
expression in human hepatoma cells.

Yeh SF, Hong CY, Huang YL, Liu TY, Choo KB, Chou CK.

Department of Medical Research, Veterans General Hospital, Taipei, Taiwan.

It has been suggested that Phyllanthus amarus may be helpful in the treatment of
hepatitis B virus infection. We studied the effect of an aqueous extract of P.
amarus on the cultured hepatoma cell line HepA2. This cell line had been
transfected with tandemly arranged HBV DNA and continued to synthesize and
secrete both HBsAg and HBeAg. Extract of P. amarus reversibly inhibited cellular
proliferation and suppressed HBsAg production but not HBeAg production in HepA2
cells. We also found that P. amarus suppressed HBsAg gene expression at mRNA
level in a time-dependent manner, and selectively abolished the HBsAg gene
promoter driven CAT activity. Our results demonstrate that P. amarus contains
some active components which can suppress the HBsAg gene expression in human
hepatoma cells. Such suppression may contribute the antiviral activity of P.
amarus in vivo.

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

PMID: 8470882 [PubMed - indexed for MEDLINE]

62: J Med Assoc Thai. 1991 Sep;74(9):381-5.

Efficacy of Phyllanthus amarus for eradication of hepatitis B virus in chronic
carriers.

Thamlikitkul V, Wasuwat S, Kanchanapee P.

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

Sixty-five adult asymptomatic chronic carriers of hepatitis B virus were
enrolled to the randomized controlled efficacy study of Phyllanthus amarus.
Thirty-four received Phyllanthus amarus 600 mg per day for 30 days and 31
received placebo in identical capsules. The conversion rate of HBsAg was 6 per
cent in the study group at day 30. When 20 subjects in the Phyllanthus amarus
group were given a further 30-day treatment and 22 placebo recipients given
Phyllanthus amarus 1,200 mg per day for 30 days, the conversion was observed in
1 (5%) in the higher dose group. Adverse effects were not observed in all
patients receiving the plant. The results indicated that Phyllanthus amarus,
whole plant except root, grown in the central part of Thailand, given at the
studied dosage and duration, had a very minimal effect on eradication of HBsAg
from Thai adult asymptomatic chronic carriers.

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

PMID: 1791391 [PubMed - indexed for MEDLINE]

63: J Hepatol. 1991 May;12(3):405-6.

Beneficial effects of Phyllanthus amarus for chronic hepatitis B, not confirmed.

Berk L, de Man RA, Schalm SW, Labadie RP, Heijtink RA.

Publication Types:
Clinical Trial
Letter
Randomized Controlled Trial

PMID: 1940272 [PubMed - indexed for MEDLINE]

64: Indian J Med Res. 1991 Mar;93:71-3.

In vitro effect of Phyllanthus amarus on hepatitis B virus.

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

Postgraduate Department of Pathology, King George's Medical College, Lucknow.

To evaluate the effects of P. amarus on hepatitis B virus (HBV) antigens and
HBV-DNA, initial ethanolic extract and subsequent fractions of the plants were
prepared. The whole plant material was dried, powdered and extracted with
alcohol and subsequently fractionated in hexane, chloroform, butanol and finally
in water. All the material were tested for in vitro effects on HBsAg, HBeAg and
HBV-DNA in serum samples positive for HBV antigens followed by the screening of
respective antigens by Elisa. HBV-DNA was determined by molecular hybridization.
The extracts were effective against HBV antigens, the butanol extract being the
most potent. Further chromatographic fractions showed an enhanced activity. The
active fractions inhibited the interaction between HBsAg/HBeAg and their
corresponding antibodies suggesting anti-HBs, anti-HBe-like activity and also an
effect on HBV-DNA.

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

PMID: 1855821 [PubMed - indexed for MEDLINE]

65: J Med Virol. 1990 Dec;32(4):212-8.

Effect of Phyllanthus amarus on duck hepatitis B virus replication in vivo.

Niu JZ, Wang YY, Qiao M, Gowans E, Edwards P, Thyagarajan SP, Gust I, Locarnini
S.

Hepatitis Research Unit, Macfarlane Burnet Centre for Medical Research,
Fairfield Hospital, Victoria, Australia.

Nine ducks congenitally infected with the duck hepatitis B virus (DHBV) were
treated either orally (four ducks for 10 weeks) or intraperitoneally (five ducks
for 12 weeks) with the Indian traditional herbal remedy Phyllanthus amarus.
Compared to placebo-treated control ducks, these treatments did not result in a
reduction of circulating viral DNA in the serum or in the level of viral DNA
replication in the liver. In two of the five intraperitoneal-treated ducks, a
reduction in the levels of duck hepatitis B surface antigenaemia (DHBsAg) was
observed. The data strongly suggest that Phyllanthus amarus has no significant
inhibitory effect on DHBV DNA replication and only a minor effect on DHBsAg
production.

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

PMID: 2081970 [PubMed - indexed for MEDLINE]

66: Lancet. 1990 Oct 13;336(8720):949-50.

Comment on:
Lancet. 1990 Jun 30;335(8705):1600-1.

Phyllanthus amarus and hepatitis B.

Thyagarajan SP, Jayaram S, Valliammai T, Madanagopalan N, Pal VG, Jayaraman K.

Publication Types:
Comment
Letter

PMID: 1976968 [PubMed - indexed for MEDLINE]

67: Lancet. 1990 Jun 30;335(8705):1600-1.

Comment in:
Lancet. 1990 Oct 13;336(8720):949-50.

Failure of Phyllanthus amarus to eradicate hepatitis B surface antigen from
symptomless carriers.

Leelarasamee A, Trakulsomboon S, Maunwongyathi P, Somanabandhu A, Pidetcha P,
Matrakool B, Lebnak T, Ridthimat W, Chandanayingyong D.

Publication Types:
Clinical Trial
Letter
Randomized Controlled Trial

PMID: 1972525 [PubMed - indexed for MEDLINE]

68: Vaccine. 1990 Mar;8 Suppl:S86-92.

Hepatitis B virus and primary hepatocellular carcinoma: treatment of HBV
carriers with Phyllanthus amarus.

Blumberg BS, Millman I, Venkateswaran PS, Thyagarajan SP.

Fox Chase Cancer Center, Philadelphia, PA.

A viricide capable of eliminating hepatitis B virus (HBV) from chronic carriers
should, theoretically, decrease the risk of primary hepatocellular carcinoma.
Extracts of Phyllanthus amarus have been shown to inhibit the DNA polymerase of
HBV and woodchuck hepatitis virus (WHV) in vitro. Three of four recently
infected WHV carriers treated i.p. with P. amarus extract lost WHV, animals
infected for greater than or equal to 3 months showed a decrease in virus
levels. Preliminary results in human carriers treated orally with P. amarus for
1 month indicated that approximately 60% of the carriers lost HBV during the
observation period.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 2158192 [PubMed - indexed for MEDLINE]

69: Cancer Detect Prev. 1989;14(2):195-201.

Hepatitis B virus and hepatocellular carcinoma--treatment of HBV carriers with
Phyllanthus amarus.

Blumberg BS, Millman I, Venkateswaran PS, Thyagarajan SP.

Fox Chase Cancer Center, Philadelphia, PA 19111.

Extracts of Phyllanthus amarus inhibit the DNA polymerase of HBV and related
viruses. Woodchuck carriers of woodchuck hepatitis virus (WHV) were treated
intraperitoneally with P. amarus extract. Three of four animals which had been
recently infected lost the virus. Animals infected for about 3 months or more
had a decrease in virus levels. Human carriers of HBV were treated orally for 1
month. About 60% of the carriers lost HBV, which did not return during the
observation period. Fractions containing active principles are now being
isolated and characterized.

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

PMID: 2559794 [PubMed - indexed for MEDLINE]

70: Lancet. 1988 Oct 29;2(8618):1017-8.

Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus.

Brook MG.

Publication Types:
Letter

PMID: 2902445 [PubMed - indexed for MEDLINE]

71: Lancet. 1988 Oct 1;2(8614):764-6.

Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus.

Thyagarajan SP, Subramanian S, Thirunalasundari T, Venkateswaran PS, Blumberg
BS.

Department of Microbiology, University of Madras, India.

In a preliminary study, carriers of hepatitis B virus were treated with a
preparation of the plant Phyllanthus amarus for 30 days. 22 of 37 (59%) treated
patients had lost hepatitis B surface antigen when tested 15-20 days after the
end of the treatment compared with only 1 of 23 (4%) placebo-treated controls.
Some subjects have been followed for up to 9 months. In no case has the surface
antigen returned. Clinical observation revealed few or no toxic effects. The
encouraging results of this preliminary study recommend continued evaluation of
this plant and the active principles isolated from it.

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

PMID: 2901611 [PubMed - indexed for MEDLINE]

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