Articles

Phyllanthus

Plant Part Used

Whole plant (excluding root)

Active Constituents

Alkaloids (including ent-norsecurinine); (1) lignans (including phyllanthine and hypophyllanthine); phenols and terpenes; bioflavonoids (including quercetin). (2)

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Phyllanthus amarus, commonly termed bahupatra or bhuiamla in the Hindu Ayurvedic system of medicine, has been traditionally used as a medicinal agent in many ethnic cultures around the world. Usually found in central and southern India, it can grow to 1-2 feet in height and have blooms with many yellow flowers. Phyllanthus species are found in other countries, including China (Phyllanthus urinaria), the Philippines, Cuba, Nigeria, and Guam.(2) Traditional uses of Phyllanthus include jaundice, gonorrhea, frequent menstruation, dysentery, and diabetes. It is used topically as a poultice for skin ulcers, sores, swelling, and itchiness. Current research with Phyllanthus species focuses on the use in viruses, specifically the hepatitis B virus.(3),(4),(21)

There is another species of Phyllanthus that is commonly used in the Ayurvedic system of medicine and should not be confused with the ones in this monograph - Phyllanthus emblica, an antioxidant and liver protective agent used in chronic pancreatitis among other conditions.

Interactions and Depletions

Interactions

  • Chemotherapy drugs ; Components of Phyllanthus have been reported in laboratory studies toimprove chemotherapy effects on cancer cells.(23)

Dosage Info

Dosage Range

200mg, 2-4 times a day.

Most Common Dosage

200mg, 3 times a day.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 3% bitter principles.

Uses

Frequently Reported Uses

  • Hepatic Cancer
  • Antiviral
  • Hepatitis (Acute, Chronic)
  • Hepatoprotective

Other Reported Uses

  • Antibacterial
  • Antimalarial

Toxicities & Precautions

General

Phyllanthus preparations are reported safe in recommended dosages.(2)

Allergy

If an allergy develops, discontinue use.

Pregnancy/ Breast Feeding

Use in pregnancy has not yet been determined.

Pharmacology

Hepatoprotection

This herb has been reported in vitro to down-regulate the transcription of hepatitis B virus mRNA.(5) Phyllanthus amarus was reported to inhibit hepatitis B virus polymerase activity, decrease episomal hepatitis B virus (HBV) DNA content, and suppress virus release into culture medium.(6),(7),(8) Phyllanthus preparations have been reported 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.(9) Preliminary human research in HBV has been conflicting.(10),(11),(12) One laboratory study reported that 60% of the carriers lost HBV during the observation period.(13) There is no data regarding Phyllanthus species in the treatment of hepatitis C. Phyllanthus may help decrease the amount of hepatitis B virus found in the blood stream, but has not been reported to remove all of the virus, however, and should not be considered a cure and medical assistance should always be sought in hepatitis infections. Phyllanthus has also been reported to have antimalarial activity in laboratory mice infected with the parasite.(14)

One study with 57 human subjects reported that the powder of Phyllanthus amarus did not significantly reduce the duration of jaundice in persons with virus B hepatitis.(15) However, there is current concern that not all species of phyllanthus have equal activity against hepatitis B, with Phyllanthus niruri and Phyllanthus urinaria having more activity than Phyllanthus amarus against hepatitis B.(16),(17)

A laboratory study with the administration of an aqueous extract of Phyllanthus amarus was found to significantly increase the survival of animals with hepatocellular carcinoma.(18) Phyllanthus amarus administration was also reported to be ineffective in controlling the liver weight, elevation of tissue gamma-glutamyl transpeptidase, serum alkaline phosphatase and serum glutamate pyruvate transaminase of hepatocellular carcinoma harboring animals. P. amarus induces the expression of caspase-3 and inhibits the expression of Bcl-2, which is an antiapoptotic protein.(23)

It was reported that carbon tetrachloride (CCl4)-induced increase of serum glutamic-pyruvic transaminase (ALT) and elevation of MDA in liver of mice are significantly lowered by Phyllanthus urinaria in vivo, and the co-incubation of isolated rat hepatocytes with Phyllanthus urinaria 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.(19) These results suggest that the anti-lipid peroxidation effect and protective action of membrane of Phyllanthus urinaria may be related to its protective action against CCl4-induced liver injuries.

Other Uses

Extracts of P. amarus have been reported in laboratory studies to prevent multi drug resistance (MDR), mainly due to its ability to synergize with the action of conventional chemotherapeutics.(22) Extracts of various Phyllanthus species have reported anti-cancer and anti-tumor activity in laboratory studies.(24)

Laboratory studies have reported that P. urinaria has antioxidant and anti-inflammatory activity.(25) P. urinaria was reported in an in vitro study to inhibit H. pylori induced inflammation in human gastric epithelial cells.(26)

An extract of P. niruri was reported to result in an increased stone-free rate that is statistically significant for lower caliceal location in patients with renal calculi.(27)

References

  1. View Abstract: Joshi BS, Gawad DH, Pelletier SW, et al. Isolation and Structure (X-ray Analysis) of Ent-norsecurinine, An Alkaloid from Phyllanthus niruri. J Nat Prod. Jul1986;49(4):614-20.
  2. View Abstract: Calixto JB, Santos AR, Cechinel Filho V, et al. A Review of the Plants of the Genus Phyllanthus: Their Chemistry, Pharmacology, and Therapeutic Potential. Med Res Rev. Jul1998;18(4):225-58.
  3. View Abstract: Thyagarajan SP, Subramanian S, Thirunalasudari T, et al. Effect of Phyllanthus amarus on Chronic Carriers of Hepatitis B Virus. Lancet. Oct1988;2(8614):764-6.
  4. View Abstract: Blumberg BS, Millman I, Venkateswaran PS, et al. Hepatitis B Virus and Hepatocellular Carcinoma--Treatment of HBV Carriers With Phyllanthus amarus. Cancer Detect Prev. 1989;14(2):195-201.
  5. View Abstract: Ott M, Thyagarajan SP, Gupta S. Phyllanthus amarus Suppresses Hepatitis B Virus by Interrupting Interactions Between HBV Enhancer I and Cellular Transcription Factors. Eur J Clin Invest. Nov1997;27(11):908-15.
  6. View Abstract: Lee CD, Ott M, Thyagarajan SP, et al. Phyllanthus amarus Down-regulates Hepatitis B Virus mRNA Transcription and Replication. Eur J Clin Invest. Dec1996;26(12):1069-76.
  7. View Abstract: Yeh SF, Hong CY, Huang YL, et al. Effect of an Extract from Phyllanthus amarus on Hepatitis B Surface Antigen Gene Expression in Human Hepatoma Cells. Antiviral Res. Mar1993;20(3):185-92.
  8. View Abstract: Jayaram S, Thyagarajan SP. Inhibition of HBsAg Secretion from Alexander Cell Line by Phyllanthus amarus. Indian J Pathol Microbiol. Jul1996;39(3):211-5.
  9. View Abstract: Wang BE. Treatment of Chronic Liver Diseases with Traditional Chinese Medicine. J Gastroenterol Hepatol. May2000;15(Suppl):E67-70.
  10. View Abstract: Doshi JC, Vaidya AB, Antarkar DS, et al. A Two-stage Clinical Trial of Phyllanthus amarus in Hepatitis B Carriers: Failure to Eradicate the Surface Antigen. Indian J Gastroenterol. Jan1994;13(1):7-8.
  11. Leelarasamee A, Trakulsomboon S, Maunwongyathi P, et al. Failure of Phyllanthus amarus to Eradicate Hepatitis B Surface Antigen from Symptomless Carriers. Lancet. Jun1990;335(8705):1600-1.
  12. Milne A, Hopkirk N, Lucas CR, et al. Failure of New Zealand Hepatitis B Carriers to Respond to Phyllanthus amarus. N Z Med J. Jun1994;107(980):243.
  13. View Abstract: Blumberg BS, Millman I, Venkatewaran PS, et al. Hepatitis B Virus and Primary Hepatocellular Carcinoma: Treatment of HBV Carriers with Phyllanthus amarus. Vaccine. Mar1990;8(Suppl):S86-92.
  14. View Abstract: Tona L, Ngimbi NP, Tsakala M, et al. Antimalarial Activity of 20 Crude Extracts from Nine African Medicinal Plants Used in Kinshasa, Congo. J Ethnopharmacol. Dec1999;68(1-3):193-203.
  15. View Abstract: Narendranathan M, Remla A, Mini PC, et al. A Trial of Phyllanthus amarus in Acute Viral Hepatitis. Trop Gastroenterol. Oct1999;20(4):164-6.
  16. View Abstract: Wang M, Cheng H, Li Y, et al. Herbs of the Genus Phyllanthus in the Treatment of Chronic Hepatitis B: Observations with Three Preparations from Different Geographic Sites. J Lab Clin Med. Oct1995;126(4):350-2.
  17. View Abstract: Mi Z, Chen H, Zhang X, et al. Screening of Antiviral Agents from Medicinal Herbs by Means of Hepadnaviruses Models. Chung Kuo Chung Yao Tsa Chih. Jan1997;22(1):43-5, 63.
  18. View Abstract: Rajeshkumar NV, Kuttan R. Phyllanthus amarus Extract Administration Increases the Life Span of Rats with Hepatocellular Carcinoma. J Ethnopharmacol. Nov2000;73(1-2):215-9.
  19. View Abstract: Zhou S, Xu C, Zhou N, et al. Mechanism of Protective Action of Phyllanthus urinaria L. Against Injuries of Liver Cells. Chung Kuo Chung Yao Tsa Chih. Feb1997;22(2):109-11
  20. Mellinger CG, Cipriani TR, Noleto GR, et al. Chemical and immunological modifications of an arabinogalactan present in tea preparations of Phyllanthus niruri after treatment with gastric fluid. Int J Biol Macromol. 15 Aug 2008;43(2):115-120. Epub  2008 Apr 8.
  21. Bagalkotkar G, Sagineedu SR, Saad MS, Stanslas J. Phytochemicals from Phyllanthus niruri Linn. and their pharmacological properties: a review. J Pharm Pharmacol. Dec 2006;58(12):1559-1570. Review.
  22. Leite DF, Kassuya CA, Mazzuco TL, et al. The cytotoxic effect and the multidrug resistance reversing action of lignans from Phyllanthus amarus. Planta Med. Dec 2006;72(15):1353-1358. Epub 2006 Oct 20.
  23. Harikumar KB, Kuttan G, Kuttan R. Phyllanthus amarus inhibits cell growth and induces apoptosis in Dalton's lymphoma ascites cells through activation of caspase-3 and down regulation of Bcl-2. Integr Cancer Ther. Jun 2009;8(2):190-194. Epub 2009 Feb 17.
  24. Huang ST, Yang RC, Lee PN, Yang SH, Liao SK, Chen TY, Pang JH. Anti-tumor and anti-angiogenic effects of Phyllanthus urinaria in mice bearing Lewis lung carcinoma. Int Immunopharmacol. Jun 2006;6(6):870-879. Epub 2006 Jan 30.
  25. Fang SH, Rao YK, Tzeng YM. Anti-oxidant and inflammatory mediator's growth inhibitory effects of compounds isolated from Phyllanthus urinaria. J Ethnopharmacol. 5 Mar 2008;116(2):333-340. Epub 2007 Dec 4.
  26. Lai CH, Fang SH, Rao YK, et al. Inhibition of Helicobacter pylori-induced inflammation in human gastric epithelial AGS cells by Phyllanthus urinaria extracts. J Ethnopharmacol. 13 Aug 2008;118(3):522-526. Epub 2008 May 28.
  27. Micali S, Sighinolfi MC, Celia A, De Stefani S, Grande M, Cicero AF, Bianchi G. Can Phyllanthus niruri affect the efficacy of extracorporeal shock wave lithotripsy for renal stones? A randomized, prospective, long-term study. J Urol. Sep 2006;176(3):1020-1022.