ABOUT PHYLLANTHUS
Pharmacology References

Clinical study

  1. Genus Phyllanthus for chronic hepatitis B virus infection: a systematic review.
    Liu J, Lin H, McIntosh H. J Viral Hepat 2001 Sep;8(5):358-66
  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. Southeast Asian J Trop Med Public Health 2001;32(1):140
  3. Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus.
    Thyagarajan SP, Subramanian S, Thirunalasundari T, Venkateswaran PS, Blumberg BS. Lancet 1988 Oct 1;2(8614):764-6
  4. Phyllanthus combination plus lamivudin in treatment of 40 cases of chronic hepatitis B.
    Zhang, JJ, Wang, HJ, Zhang, H. Journal of Shandong University of TCM, China

     

Laboratory Research paper
  1. A review of the plants of the genus Phyllanthus: their chemistry, pharmacology, and therapeutic potential.
    Calixto JB, Santos AR, Cechinel Filho V, Yunes RA. Med Res Rev 1998 Jul;18(4):225-58
  2. Treatment of chronic liver diseases with traditional Chinese medicine.
    Wang BE. J Gastroenterol Hepatol 2000 May;15 Suppl:E67-70
  3. Screening of antiviral agents from medicinal herbs by means of Hepadnaviruses models
    Mi Z, Chen H, Zhang X, Li Z, Chen W, Shao X. Zhongguo Zhong Yao Za Zhi 1997 Jan;22(1):43-5, 63
  4. The in-vitro inactivation of HBsAg by extracts of plants in the genus Phyllanthus
    del Barrio Alonso G, Caballero Perez O, Chevalier P. Rev Cubana Med Trop 1995;47(2):127-30
  5. Phyllanthus amarus suppresses hepatitis B virus by interrupting interactions between HBV enhancer I and cellular transcription factors.
    Ott M, Thyagarajan SP, Gupta S. Eur J Clin Invest 1997 Nov;27(11):908-15
  6. Phyllanthus amarus down-regulates HBV mRNA transcription and replication.
    Lee CD, Ott M, Thyagarajan SP, Shafritz DA, Burk RD, Gupta S. Eur J Clin Invest 1996 Dec;26(12):1069-76
  7. Inhibition of HBsAg secretion from Alexander cell line by Phyllanthus amarus.
    Jayaram S, Thyagarajan SP. Indian J Pathol Microbiol 1996 Jul;39(3):211-5
  8. Experimental study on anti-duck hepatitis B viral effect of Phyllanthus urinaria of different areas and combined therapy with other drugs
    Chen YX, Guo SH, Zhang DF. Zhongguo Zhong Xi Yi Jie He Za Zhi 1995 Apr;15(4):225-7
  9. Evaluation of anti-hepadnavirus activity ofPhyllanthus amarus and Phyllanthus maderaspatensis in duck hepatitis B virus carrier Pekin ducks.
    Munshi A, Mehrotra R, Ramesh R, Panda SK. J Med Virol 1993 Dec;41(4):275-81
  10. Effects of extract from Phyllanthus urinaria on HBsAg production in PLC/PRF/5 cell line
    Ji XH, Qin YZ, Wang WY, Zhu JY, Liu XT. Zhongguo Zhong Yao Za Zhi 1993 Aug;18(8):496-8, 511
  11. 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. Antiviral Res 1993 Mar;20(3):185-92
  12. Effects of Phyllanthus plant extracts on duck hepatitis B virus in vitro and in vivo.
    Shead A, Vickery K, Pajkos A, Medhurst R, Freiman J, Dixon R, Cossart Y. Antiviral Res 1992 Jun;18(2):127-38
  13. In vitro effect of Phyllanthus amarus on hepatitis B virus.
    Mehrotra R, Rawat S, Kulshreshtha DK, Goyal P, Patnaik GK, Dhawan BN. Indian J Med Res 1991 Mar;93:71-3
  14. 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. J Med Virol 1990 Dec;32(4):212-8
  15. In vitro studies on the effect of certain natural products against hepatitis B virus.
    Mehrotra R, Rawat S, Kulshreshtha DK, Patnaik GK, Dhawan BN. Indian J Med Res 1990 Apr;92:133-8
  16. HBV and hepatocellular carcinoma-treatment of HBV carriers with Phyllanthus amarus.
    Blumberg BS, Millman I, Venkateswaran PS, Thyagarajan SP. Cancer Detect Prev 1989;14(2):195-201
  17. Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies.
    Venkateswaran PS, Millman I, Blumberg BS. Proc Natl Acad Sci U S A 1987 Jan;84(1):274-8
  18. In Vitro Inactivation of HbsAg. by Eclipta alba Hassk and Phyllanthus niruri.
    Indian J Med Res 76 (Suppl) Dec 1982, 124-30.
  19. Comparative hepatoprotective activity of three Phyllanthus Species, P. urinaria, P. niruri and P. simplex, on carbon tetrachloride-induced liver injury in the rat
    A. Prakash, K.S. Satyan, S.P. Wahi, and R.P. Singh. Phototherapy Research Vol. 9, 594-596, 1995.
  20. Effect of Emblica officinalis, Phyllanthus amarus and Picrorrhiza kurroa on N-nitrosodiethylamine induced hepatocarcinogenesis.
    Jeena KJ, Joy KL, Kuttan R. Cancer Lett 1999 Feb 8;136(1):11-6
  21. Effects of Phyllanthus urinaria L. on human hepatoma cells.
    Wang CJ, Yuan DP, Chen W, et al. Shenzen J. of Traditional Chinese Medicine Research. 1997. Vol. 8 (6): 499
  22. General studies of Chinese medicine and its active ingredient in anti-viral hepatitis.
    Shee Kan & She RH. Chinese Herbal Medicine. 1994. Vol. 25(7): 381-2
  23. Herbal medicines for liver diseases in India.
    Thyagarajan S, Jayaram S, Gopalakrishnan V, Hari R, Jeyakumar P, Sripathi M. J Gastroenterol Hepatol 2002 Dec;17 Suppl 3:S370-S376
  24. Mechanism of protective action of Phyllanthus against injuries of liver cells.
    Zhou S, Xu C, Zhou N, Huang Y, Huang , et al. Zhongguo Zhong Yao Za Zhi 1997 Feb;22(2):109-11
  25. Phyllanthus amarus extract administration increases the life span of rats with hepatocellular carcinoma.
    Rajeshkumar NV, Kuttan R. J Ethnopharmacol 2000 Nov;73(1-2):215-9
  26. Protective effect of Phyllanthus against CCl4 -induced mitochondrial dysfunction.
    Padma P, Setty OH. Life Sci 1999;64(25):2411-7
  27. Protective effect of Phyllanthus against ethanol-induced mitochondrial dysfunction.
    Sebastian T, Setty OH. Alcohol 1999 Jan;17(1):29-34
  28. Screening of Phyllanthus niruri Linn. And Ricinus communis Linn. On alcohol-induced liver cell damage in non-hepatomized and partially hepatictomized rats.
    Shyam SA, Arun G & Sarla, A. Indian J. of Pharmacology. 1986. 18(14): 211-214.
  29. Study of Phyllanthus product inhibition effect on mice liver cancer.
    Yang SL, Guang SH & Zhu YT. Journal of Cancer. 2000. Vol. 19(8) 837-838.

     

Traditionally uses
  1. A survey of medicinal plants of Minas Gerais, Brazil
    G. Schmeda Hirschmann and A. Rojas de Arias. Jour of Ethnopharm, 29, 1990, 159-172.
  2. Amazonian Ethnobotanical Dictionary
    James Alan Duke and Rodolfo Vasquez, 1994, by CRC Press.
  3. Antihepatotoxic principles of Phyllanthus niruri herbs.
    Syamasundar KV, Singh B, Thakur RS, Husain A, Kiso Y, Hikino H.
  4. Usage and bioassays in Phyllanthus. IV. Clustering of antiviral uses and other effects.
    Unander DW, Webster GL, Blumberg BS. J Ethnopharmacol 1995 Jan;45(1):1-18

Clinical study

1.Genus Phyllanthus for chronic hepatitis B virus infection: a systematic review.
Liu J, Lin H, McIntosh H. J Viral Hepat 2001 Sep;8(5):358-66

Twenty-two randomized trials (n=1947) were identified. The methodological quality was high in five double-blind trials and low in the 17 remaining trials. The combined results showed that Phyllanthus species had positive effect on clearance of serum HBsAg (relative risk 5.64, 95% CI 1.85-17.21) compared with placebo or no intervention. Phyllanthus species were better than nonspecific treatment or other herbal medicines for the clearance of serum HBsAg, HBeAg, HBV DNA, and liver enzyme normalization. No serious adverse event was reported...

 

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

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.

 

3. Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus.
Thyagarajan SP, Subramanian S, Thirunalasundari T, Venkateswaran PS, Blumberg BS. Lancet 1988 Oct 1;2(8614):764-6

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.

 

4. Phyllanthus combination plus lamivudin in treatment of 40 cases of chronic hepatitis B.
Zhang, JJ, Wang, HJ, Zhang, H. Journal of Shandong University of TCM, China

Phyllanthus niruri has been demonstrated to have inhibition effect on HBV replication, increases immune system, significantly reduce enzymes levels due to CCl4-induced liver injury, inhibits liver free radical formation and repair liver cells. Phyllanthus has stronger effect on immune system and liver function but not so effective against HBV replication. Combination of both treatments can lead to a synergetic effect and result has showed that the PHCo plus lamivudin has a better effect compared to lamivudin alone

 

Laboratory Research paper
  1. A review of the plants of the genus Phyllanthus: their chemistry, pharmacology, and therapeutic potential.
    Calixto JB, Santos AR, Cechinel Filho V, Yunes RA. Med Res Rev 1998 Jul;18(4):225-58

    The plants of the genus Phyllanthus are widely distributed in most tropical and subtropical countries, and have long been used in folk medicine to treat kidney and urinary bladder disturbances, intestinal infections, diabetes, and hepatitis B. Recently, the interest in the plants has increased considerably. Substantial progress on their chemical, pharmacological properties, and a few clinical studies of some Phyllanthus species have been made. This review discusses the current knowledge of their chemistry, the in vitro and in vivo pharmacological, biochemical, and clinical studies carried out on the extracts, and the main active constituents isolated from different species of plants of the genus Phyllanthus. These studies carried out with the extracts and purified compounds from these plants support most of their reported uses in folk medicine as an antiviral, in the treatment of genitourinary disorders, and as antinociceptive agents. Several compounds including alkaloids, flavonoids, lignans, phenols, and terpenes were isolated from these plants and some of them interact with most key enzymes. Together this data strongly supports the view that Phyllanthus have potential beneficial therapeutic actions in the management of hepatitis B, nefrolitiase, and in painful disorders.

  2. Treatment of chronic liver diseases with traditional Chinese medicine.
    Wang BE. J Gastroenterol Hepatol 2000 May;15 Suppl:E67-70

    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.

  3. Screening of antiviral agents from medicinal herbs by means of Hepadnaviruses models
    Mi Z, Chen H, Zhang X, Li Z, Chen W, Shao X. Zhongguo Zhong Yao Za Zhi 1997 Jan;22(1):43-5, 63

    The antiviral study of 21 Chinese medicinal herbs was carried out in vitro and in vivo. The extracts of Phyllanthus urinarin and Polygonum cuspidatum exhibite obvious effects on duck hepatitis B virus and human hepatitis B virus, while the extract of Eclipta alba showed limited inhibition on HBV DAN polymerase.

  4. The in-vitro inactivation of HBsAg by extracts of plants in the genus Phyllanthus
    del Barrio Alonso G, Caballero Perez O, Chevalier P. Rev Cubana Med Trop 1995;47(2):127-30

    Three species from the Phyllanthus genus coming from the Cuban eastern zone were studied to determine the inactivation capacity of the surface antigen (Ags HB) of in vitro hepatitis B virus. Alcoholic extracts were prepared from each species and from different parts of such plants, and sera from patients positive to Ags HB were treated with them. Results demonstrate that the analysed species own the capacity of inactivating that antigen between the 93 and the 97% of the sera assayed. The inactivation capacity analysis of the three parts of Phyllanthus chamaecristoides revealed a greater activity in extracts from the stems (97%) with a behavior resembling the two incubation temperatures used. The presence of flavonoids in the extract of this species is observed.

  5. Phyllanthus amarus suppresses hepatitis B virus by interrupting interactions between HBV enhancer I and cellular transcription factors.
    Ott M, Thyagarajan SP, Gupta S. Eur J Clin Invest 1997 Nov;27(11):908-15

    The Phyllanthus amarus plant suppresses HBV mRNA transcription in vitro and exhibits therapeutic potential in chronic HBV carriers. 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.

  6. Phyllanthus amarus down-regulates HBV mRNA transcription and replication.
    Lee CD, Ott M, Thyagarajan SP, Shafritz DA, Burk RD, Gupta S. Eur J Clin Invest 1996 Dec;26(12):1069-76

    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.

  7. Inhibition of HBsAg secretion from Alexander cell line by Phyllanthus amarus.
    Jayaram S, Thyagarajan SP. Indian J Pathol Microbiol 1996 Jul;39(3):211-5

    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 P. amarus. Aquous extract of P. 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.

  8. Experimental study on anti-duck hepatitis B viral effect of Phyllanthus urinaria of different areas and combined therapy with other drugs
    Chen YX, Guo SH, Zhang DF. Zhongguo Zhong Xi Yi Jie He Za Zhi 1995 Apr;15(4):225-7

    The duck hepatitis B virus model was treated with Phyllanthus urinaria of different area and combined with Sophora flavesceus as well as ciprofloxacin once a day for one month, the results indicated: Guangxi and Yunnan Phyllanthus could lower the serum DHBV DNA significantly (P < 0.05), but Chongqing Phyllanthus couldn't. And the amount of serum DHBV DNA rose a week after stopping of Yunnan Phyllanthus. The antiviral effect of Guangxi Phyllanthus combined with ciprofloxacin seems to be strengthened (P < 0.05).

  9. Evaluation of anti-hepadnavirus activity ofPhyllanthus amarus and Phyllanthus maderaspatensis in duck hepatitis B virus carrier Pekin ducks.
    Munshi A, Mehrotra R, Ramesh R, Panda SK. J Med Virol 1993 Dec;41(4):275-81

    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.

  10. Effects of extract from Phyllanthus urinaria on HBsAg production in PLC/PRF/5 cell line
    Ji XH, Qin YZ, Wang WY, Zhu JY, Liu XT. Zhongguo Zhong Yao Za Zhi 1993 Aug;18(8):496-8, 511

    Experiment on the effect of extracts from P. urinaria on HBsAg production in PLC/PRF/5 human hepatoma cell line showed that the production was decreased markedly 48 hours after the treatment of cells with 2-4 mg/ml P. urinaria, especially in combination with 10(-5) mol/L of Ara-A. The decrease of extracellular HB-sAg excretion seems to stem from the inhibition of intracellular HBsAg formation.

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

    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.

  12. Effects of Phyllanthus plant extracts on duck hepatitis B virus in vitro and in vivo.
    Shead A, Vickery K, Pajkos A, Medhurst R, Freiman J, Dixon R, Cossart Y. Antiviral Res 1992 Jun;18(2):127-38

    The effects of extracts of five Australian Phyllanthus species (P. hirtellus, P. gunnii, P. gasstroemii, P. similis and P. tenellus), other plant extracts and the antiviral drug foscarnet on duck hepatitis B virus (DHBV) endogenous DNA polymerase (DNAp) activity were compared. All 5 Phyllanthus species caused 50% inhibition at concentrations of dry weight between 350-800 micrograms/ml, which is comparable with the effect described for P. amarus on the DNAp of human and woodchuck hepatitis B viruses. Incubation of P. hirtellus with 100 ID50 DHBV neutralized infection. However, neither P. gasstroemi extract, given by intraperitoneal injection (i.p.) at a dose of 20 mg/kg 3 times per week to ducklings early in the incubation period, or P. hirtellus extract, given to established DHBV carrier ducklings, prevented or eliminated infection.

  13. In vitro effect of Phyllanthus amarus on hepatitis B virus.
    Mehrotra R, Rawat S, Kulshreshtha DK, Goyal P, Patnaik GK, Dhawan BN. Indian J Med Res 1991 Mar;93:71-3

    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.

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

    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.

  15. In vitro studies on the effect of certain natural products against hepatitis B virus.
    Mehrotra R, Rawat S, Kulshreshtha DK, Patnaik GK, Dhawan BN. Indian J Med Res 1990 Apr;92:133-8

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

  16. HBV and hepatocellular carcinoma-treatment of HBV carriers with Phyllanthus amarus.
    Blumberg BS, Millman I, Venkateswaran PS, Thyagarajan SP. Cancer Detect Prev 1989;14(2):195-201

    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.

  17. Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies.
    Venkateswaran PS, Millman I, Blumberg BS. Proc Natl Acad Sci U S A 1987 Jan;84(1):274-8

    An aqueous extract of the plant Phyllanthus niruri inhibits endogenous DNA polymerase of hepatitis B virus and binds to the surface antigen of hepatitis B virus in vitro. The extract also inhibits woodchuck hepatitis virus (WHV) DNA polymerase and binds to the surface antigen of WHV in vitro. The extract, nontoxic to mice, was tested for antiviral activity in woodchucks (Marmota monax). In a trial using six long-term WHV-carrier woodchucks, five treated animals showed a faster decrease in woodchuck hepatitis virus surface antigen titer compared to one untreated control. In animals recently infected with WHV, the extract was effective when administered i.p. in three out of four animals in reducing and within 3-6 weeks eliminating both the surface antigen titer and DNA polymerase activity in serum. The treatment was discontinued after 10 weeks, and the treated animals have remained free of detectable markers of WHV for more than 45 weeks. In contrast, three untreated controls remained positive for both markers for WHV. One of the controls died after 8 weeks; the other two controls have remained positive for WHV markers for more than 45 weeks. In a third trial with long-term carriers, test animals treated subcutaneously with the extract for 12 weeks did not respond; but on switching the mode of administration to i.p., two out of the five animals showed a significant decrease in woodchuck hepatitis virus surface antigen titer compared to controls.

  18. In Vitro Inactivation of HbsAg. by Eclipta alba Hassk and Phyllanthus niruri.
    Indian J Med Res 76 (Suppl) Dec 1982, 124-30.

    Researchers did an in vitro test to evaluate the in vitro immuno-inactivating ability of plants on hepatitis B surface antigen. When P. niruri roots and shoots were dried and powdered, the researchers revealed a definite immunoinactive property of the plant against the surface antigen of hepatitis B virus. Further analysis by TLC indicated a red pigment uniformly present in all the parts of these plants to be the seat of such action.

  19. Comparative hepatoprotective activity of three Phyllanthus Species, P. urinaria, P. niruri and P. simplex, on carbon tetrachloride-induced liver injury in the rat
    A. Prakash, K.S. Satyan, S.P. Wahi, and R.P. Singh. Phototherapy Research Vol. 9, 594-596, 1995.

    Pretreatment of animals with an alcoholic extract of P. niruri showed it had significant hepatoprotective activity at doses of 40mg/kg/day (p less than 0.05) and 400 mg/kg/day (p < 0.01). Further, at the different doses administered, the extracts showed dose-dependent hepatoprotective activity.

  20. Effect of Emblica officinalis, Phyllanthus amarus and Picrorrhiza kurroa on N-nitrosodiethylamine induced hepatocarcinogenesis.
    Jeena KJ, Joy KL, Kuttan R. Cancer Lett 1999 Feb 8;136(1):11-6

    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.

  21. Effects of Phyllanthus urinaria L. on human hepatoma cells.
    Wang CJ, Yuan DP, Chen W, et al. Shenzen J. of Traditional Chinese Medicine Research. 1997. Vol. 8 (6): 499

    The effects of Phyllanthus urinaria L. on SMMC7221 of human hepatoma cells were studied. Human hepatoma cells were treated with extractive of P. urinaria L. in vitro. The survival activity and DNA synthesis of the cells were observed by MTT assay and H-TdR incorporating test. Results showed after treated with the extractive of P. urinaria, the survival activities of SMMC7221 cells were obviously weakened and incorporation rates of H-TdR decreased significantly, the inhibitory rates on cell proliferation increased dose-dependently. P. urinaria therefore had remarkable effects of inhibition on poliferation as well as toxicities on human hepatoma cells.

  22. General studies of Chinese medicine and its active ingredient in anti-viral hepatitis.
    Shee Kan & She RH. Chinese Herbal Medicine. 1994. Vol. 25(7): 381-2

    Studies have shown Phyllanthus species are effective in preventing hepatitis, liver cell protection and liver cancer prevention. In vitro studies exhibit HBsAg inactivation activity as well as HBV DNA, WHV DNA and DHBV DNAp inhibition activities.

  23. Herbal medicines for liver diseases in India.
    Thyagarajan S, Jayaram S, Gopalakrishnan V, Hari R, Jeyakumar P, Sripathi M. J Gastroenterol Hepatol 2002 Dec;17 Suppl 3:S370-S376

    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. 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 HBV and HVC, 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.

  24. Mechanism of protective action of Phyllanthus against injuries of liver cells.
    Zhou S, Xu C, Zhou N, Huang Y, Huang , et al. Zhongguo Zhong Yao Za Zhi 1997 Feb;22(2):109-11

    It has been found out that the carbon tetrachloride (CCl4)-induced increase of serum glutamic-pyruvic transaminase (ALT) and elevation of MDA in liver of mice are significantly lowered by Phyllanthus in vivo, and the coincubation of isolated rat hepatocytes with Phyllanthus in vitro significantly inhibits CCl4-induced decrease of mobility of membrane of liver cells and increase of intracellular free Ca2+ ([Ca2+]i) concentrations of liver cells. These results suggest that the anti-lipid peroxidation effect and protective action of membrane of Phyllanthus may be related to its protective action against CCl4-induced liver injuries.

  25. Phyllanthus amarus extract administration increases the life span of rats with hepatocellular carcinoma.
    Rajeshkumar NV, Kuttan R. J Ethnopharmacol 2000 Nov;73(1-2):215-9

    The effect of P. 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. 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.

  26. Protective effect of Phyllanthus against CCl4 -induced mitochondrial dysfunction.
    Padma P, Setty OH. Life Sci 1999;64(25):2411-7

    The effect of CCl4 administration on liver mitochondrial function and the protective effect of an aqueous extract of Phyllanthus were studied in rats. The following changes were observed in mitochondria due to the administration of CCl4. 1) A decrease in the rate of respiration, respiratory control ratio and P/O ratio using glutamate and malate or succinate as substrates. 2) A decrease in the activities of NADH dehydrogenase (35%), succinate dehydrogenase (76%) and cytochrome c oxidase (51%). The rate of electron transfer through site I, site II and site III was studied independently and found to be significantly decreased. 3) A decrease in the content of cytochrome aa3 (34%). 4) A significant decrease in the levels of phospholipids particularly cardiolipin and a significant increase in the lipid peroxide level was observed. The CCl4 induced toxicity may be partly due to the lipid peroxidation and partly due to the effect on protein synthesis. Administration of rats with an aqueous extract of Phyllanthus prior to CCl4 administration showed significant protection on the carbon tetrachloride induced mitochondrial dysfunction on all the parameters studied.

  27. Protective effect of Phyllanthus against ethanol-induced mitochondrial dysfunction.
    Sebastian T, Setty OH. Alcohol 1999 Jan;17(1):29-34

    Chronic ethanol consumption (10 g per kg body weight) significantly decreased the rate of respiration, P/O ratio, and respiratory control ratio (RCR). The activities of NADH dehydrogenase and cytochrome oxidase were significantly decreased in submitochondrial particles by ethanol administration compared to control. No significant difference was observed in membrane potential of submitochondrial particles. Cytochrome b, c and aa3 content of mitochondria were significantly decreased by ethanol feeding. Ethanol-induced inhibition on rate of respiration, P/O ratio, and RCR was relieved to a great extent by the administration of the aqueous extract of Phyllanthus (100 mg dry powder of the plant per kg body weight) along with ethanol.

  28. Screening of Phyllanthus niruri Linn. And Ricinus communis Linn. On alcohol-induced liver cell damage in non-hepatomized and partially hepatictomized rats.
    Shyam SA, Arun G & Sarla, A. Indian J. of Pharmacology. 1986. 18(14): 211-214.

    A new model of short duration for inducing hepatotoxicity in rat has been developed by administrating Tohfa' a country made liquor (28.5% of ethanol) to partially hepatectomized (65-70%) rats orally, daily for ten days. Fatty changes were taken as an index of hepatoxicity because other changes namely fibrosis and cirrhosis cannot be produced in rats. Biochemical and hispathological studies revealed that 50% alchoholic extract of roots and leaves of P. niruri (PN), commonly known as Jaramala in Hindi, has got hepatoprotective effect on alcohol induced liver cell damage in non-hepatectomised and partially hepatetomised rats. The root extract of PN was found to be more effective hepatoprotective agent than the leaves extract. 50% of alcoholic extract of leaves of Ricinus communis (RC) commonly known as Arand in Hindi, did not shoe any significant hepatoprotective activity.

  29. Study of Phyllanthus product inhibition effect on mice liver cancer.
    Yang SL, Guang SH & Zhu YT. Journal of Cancer. 2000. Vol. 19(8) 837-838.

    Study showed a Chinese medicine with Phyllanthus as chief ingredient has an inhibition effect on mice transplanted liver cancer. It showed better effect as compared to BCG.

 

Traditionally uses
  1. A survey of medicinal plants of Minas Gerais, Brazil
    G. Schmeda Hirschmann and A. Rojas de Arias. Jour of Ethnopharm, 29, 1990, 159-172.

    Historically, Phyllanthus infusion or decoction is taken to treat renal diseases. It dissolves kidney and bladder stones. The roots are used for jaundice.

  2. Amazonian Ethnobotanical Dictionary
    James Alan Duke and Rodolfo Vasquez, 1994, by CRC Press.

    Phyllanthus niruri is considered digestive, diuretic, emmenagogue, laxative, stomachic, tonic and vermifuge. Has proven antihepatotoxic, antispasmodic, antiviral, bactericidal, diuretic, febrifugal, and hypoglycemic activity.

  3. Antihepatotoxic principles of Phyllanthus niruri herbs.
    Syamasundar KV, Singh B, Thakur RS, Husain A, Kiso Y, Hikino H.

    Among phyllanthin, hypophyllanthin, triacontanal and tricontanol isolated from a hexane extract of Phyllanthus niruri, phyllanthin and hypophyllanthin protected against carbon tetrachloride- and galactosamine-induced cytotoxicity in primary cultured rat hepatocytes, while triacontanal was protective only against galactosamine-induced toxicity.

  4. Usage and bioassays in Phyllanthus. IV. Clustering of antiviral uses and other effects.
    Unander DW, Webster GL, Blumberg BS. J Ethnopharmacol 1995 Jan;45(1):1-18

    A number of species of the genus Phyllanthus have been tested for their efficacy as antivirals, partly on the basis of references to traditional usage for the treatment of diseases possibly having a viral origin. Consideration of the data from ethnobotany, in vitro assays and clinical trials supported the presence of some type of biological activity particularly within the subgenus Phyllanthus. Although the herbaceous species of subgenus Phyllanthus have been extensively used to treat jaundice, and have generally inhibited hepadnavirus DNAP.

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