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Phyllanthus
 

Phyllanthus Introduction

Phyllanthus amarus, or niruri, is the plant commonly referred to as Phyllanthus or Bhumyamalaki. It is a member of the Euphorbiaceae family. [1] The leaves and other aerial portions of the plant are used medicinally.

Phyllanthus has a long history of use in Southeast Asia. It has also been used as part of Ayurvedic medicine, the traditional system of medicine in India. Historically, Phyllanthus was used as a supportive herb; assisting with circulatory, digestive, and skeletal system function. [2] In addition, Phyllanthus is considered one of the best herbs for treating liver disorders.

The main constituents in Phyllanthus include; lignans (phyllanthine and hypophyllanthine), alkaloids, bioflavonoids (quercetin), and repandusinic acid. Repandusinic acid, has been shown to have anti-viral properties in vitro, inhibiting HIV and HTLV-I replication; this agent also has HIV reverse transciptase activity. [3]

Pharmacologic activity of Phyllanthus includes anti-viral, anti-inflammatory, and hepatoprotective activity. It also harnesses the ability to block DNA polymerase, the enzyme needed for the hepatitis B virus to reproduce. [4]

Aqueous and hexane extracts of Phyllanthus have demonstrated the ability to inhibit nitric oxide (NO) and prostaglandin E2 (PGE2), attenuation of tumor necrosis factor-alpha (TNF-alpha), endotoxin-induced nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and inhibited NF-kappa-B production in vitro as well. [5] The same extracts inhibited induction of interleukin (IL)-1beta, IL-10, and interferon-gamma in human whole blood and reduced TNF-alpha production in vivo.

Mild hepatoprotective effects have been shown in in vitro tests. A study using rats demonstrated a normalizing effect on fatty deposition in the liver after alcohol ingestion. As well, Phyllanthus can inhibit angiotensin-converting enzyme. [6]

Medicinal actions ascribed to Phyllanthus:

  • hepatoprotective
  • antiviral
  • hypoglycemic
  • alterative
  • cholagogue
  • vulerary
  • diuretic
  • antioxidant

Phyllanthus has also been employed for specific liver dysfunctions, skin rashes, pruritis (itching), and “blood deficiency.”

Phyllanthus Uses

The main application of Phyllanthus receiving the most attention is viral infection of the liver, specifically hepatitis B. Over the years, there have been numerous trials with conflicting results; some showing no effect and some showing profound effects. [7-10] A review of randomized clinical trials conducted in 2001 by the Cochrane Hepato-biliary Group concluded that Phyllanthus species may have a positive effect on antiviral activity and liver biochemistry in chronic HBV infection. [11] However, they stated that the evidence is not strong due to the general low methodological quality and variations of the herb; the researchers indicated that larger, more rigorously monitored trials are needed.

As mentioned, the anti-viral effects of Phyllanthus appear to apply to HIV as well. A recent study demonstrated the efficacy of a water/alcohol extract of P. amarus in blocking HIV-1 attachment and the HIV-1 enzymes integrase, reverse transcriptase, and protease. [12] Furthermore, when administered to HIV positive individuals, sera at a final concentration of 5% reduced HIV replication by more than 30%. Phyllanthus also has the ability to inhibit the replication of a variety of (reverse transcriptase) RT inhibitor-resistant HIV-1 strains. [13]

Phyllanthus has also demonstrated effectiveness in treating diabetes in some studies, but failed to show effect in others. A study conducted among nine mild hypertensives (four of them also suffering from diabetes mellitus) examined the effect of a preparation of the whole plant of P. amarus over a 10 day period. [14] The results showed a significant increase in 24 hour urine volume, urine and serum sodium levels; a significant reduction in systolic blood pressure in non-diabetic hypertensives and female subjects; and significantly reduced plasma glucose.

The authors concluded that P. amarus is a potential diuretic, hypotensive, and hypoglycaemic drug for humans. An animal study also found that a methanol extract of Phyllanthus amarus reduces plasma glucose. [15] However, a one week long trial of a Phyllanthus amarus extract in patients with non-insulin dependent diabetes mellitus (NIDDM) did not result in any significant change in plasma glucose levels. [16] Large scale double-blind, controlled trials are required to determine whether Phyllanthus is an effective hypoglycemic agent.

Phyllanthus may also be of benefit as an adjunctive treatment for certain forms of cancer. Phyllanthus extracts have shown anticarcinogenic and antimutagenic activity both in vivo and in vitro. [17-19] One particular animal study showed that a Phyllanthus amarus extract 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; all of which were reduced by radiation treatment. [20] This may prove relevant in reducing radiation-induced cellular damage.

Finally, phyllanthus may be useful for patients with gastric lesions, neuropathic chronic pain, hypertension, diarrhea, and gastrointestinal complaints. [14, 21-23]

Phyllanthus Dosages

Dosages are dependent on the type of preparation and the intended condition to be treated. Generally, if using a 1:2 strength tincture, the dosage range is 0.2 - 3.0 milliliters, three times daily. For whole powder forms, the dose is 250 milligrams to 1 gram daily. Phyllanthus may also be used externally as a poultice to treat skin conditions.

Phyllanthus Toxicities and Contraindications

In terms of Ayurvedic medicine, Phyllanthus should be used with caution in the constitutional category, Vata. Phyllanthus may interact with diabetic medications due to its hypoglycemic effect, and should be used with extreme caution in these individuals. [24]

A Phyllanthus dose of 100 mg/kg body weight, administered orally for 30 days, was investigated in cyclic adult female mice. [25] There were no significant changes in absolute body and organ weights, and no effect on hematological and clinical biochemical tests. Phyllanthus is considered non-toxic. However, cohabited females with normal male mice were unable to become pregnant as their cyclicity was affected, indicating a contraceptive effect. This effect was reversed upon discontinuation of the extract. Therefore, Phyllanthus should not be used if women who are trying to conceive.

References

1. Botanical Medicine Class Notes. Bastyr University, Kenmore, WA. 2002.

2. Frawley D and Lad V. The Yoga of Herbs, 2nd Ed. Lotus Press, Twin Lakes, WI 2001:248.

3. Yeh et al. Antiviral Res 1993;20:185

4. Meixa W et al. Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B: observation with three preparations from different geographic sites. J Lab Clin Med 1995;126:350–352.

5. Kiemer AK et al. Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX-2, and cytokines via the NF-kappaB pathway. J Hepatol 2003;38(3):289-97.

6. Mills S and Bone K. Principles and Practice of Phytotherapy. Churchill Livingstone, Edinburgh, UK 2000:191.

7. Xin-Hua W et al. A comparative study of Phyllanthus amarus compound and interferon in the treatment of chronic viral hepatitis B. Southeast Asian J Trop Med Public Health. 2001;32(1):140-2.

8. Narendranathan M et al. A trial of Phyllanthus amarus in acute viral hepatitis.Trop Gastroenterol. 1999;20(4):164-6.

9. Blumberg BS et al. Hepatitis B virus and hepatocellular carcinoma–treatment of HBV carriers with Phyllanthus amarus. Cancer Detect Prev. 1989;14(2):195-201.

10. Thyagarajan SP et al. Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus.Lancet. 1988;2(8614):764-6.

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

12. Notka F, Meier G, Wagner R. Concerted inhibitory activities of Phyllanthus amarus on HIV replication in vitro and ex vivo. Antiviral Res. 2004;64(2):93-102.

13. Notka F, Meier GR, Wagner R. Inhibition of wild-type human immunodeficiency virus and reverse transcriptase inhibitor-resistant variants by Phyllanthus amarus. Antiviral Res. 2003;58(2):175-86.

14. Srividya N, Periwal S. Diuretic, hypotensive and hypoglycaemic effect of Phyllanthus amarus. Indian J Exp Biol. 1995;33(11):861-4.

15. Raphael KR, Sabu MC, Kuttan R. Hypoglycemic effect of methanol extract of Phyllanthus amarus Schum & Thonn on alloxan induced diabetes mellitus in rats and its relation with antioxidant potential. Indian J Exp Biol. 2002;40(8):905-9.

16. Moshi MJ et al. The effect of Phyllanthus amarus aqueous extract on blood glucose in non-insulin dependent diabetic patients. Phytother Res. 2001;15(7):577-80.

17. Rajeshkumar NV et al. Antitumour and anticarcinogenic activity of Phyllanthus amarus extract. J Ethnopharmacol. 2002;81(1):17-22.

18. Sripanidkulchai B et al. Antimutagenic and anticarcinogenic effects of Phyllanthus amarus.Phytomedicine. 2002;9(1):26-32.

19. Raphael KR et al. Anti-mutagenic activity of Phyllanthus amarus Schum & Thonn in vitro as well as in vivo. Teratog Carcinog Mutagen. 2002;22(4):285-91.

20. Kumar KB, Kuttan R. Protective effect of an extract of Phyllanthus amarus against radiation-induced damage in mice. J Radiat Res (Tokyo). 2004;45(1):133-9.

21. Raphael KR, Kuttan R. Inhibition of experimental gastric lesion and inflammation by Phyllanthus amarus extract. J Ethnopharmacol. 2003;87(2-3):193-7.

22. Kassuya CA et al. Anti-allodynic and anti-oedematogenic properties of the extract and lignans from Phyllanthus amarus in models of persistent inflammatory and neuropathic pain. Eur J Pharmacol. 2003;478(2-3):145-53.

23. Odetola AA, Akojenu SM. Anti-diarrhoeal and gastro-intestinal potentials of the aqueous extract of Phyllanthus amarus (Euphorbiaceae).Afr J Med Med Sci. 2000;29(2):119-22.

24. Brinker F. Herb Contraindications and Drug Interactions. Eclectic Medical Publications, Sandy, OR 1998:166

25. Rao MV, Alice KM. Contraceptive effects of Phyllanthus amarus in female mice. Phytother Res. 2001;15(3):265-7.