Antiviral Properties
One of the most impressive applications of PN is in the treatment of certain viruses, particularly hepatitis B. Hepatitis B is a virus that affects the liver, causing inflammation and jaundice, possibly leading to liver cirrhosis, cancer, or even death. Many people will clear the infection on their own after a few weeks, but others, especially children, will be unable to eliminate the virus, and will suffer from chronic hepatitis. The chronic form of the virus may manifest as an asymptomatic "carrier state" or may be associated with constant liver inflammation. Infection with hepatitis B is always associated with the presence of a certain surface antigen on the liver cells called Hep B Surface Antigen or HBsAg. Both In-vitro and In-vivo studies have reported that PN exhibits marked anti-HBsAg activity on the surface of liver cells. In another study, 37 patients with chronic viral hepatitis B were treated with a daily dose of 600mg of PN for 30 days. 59% of the patients showed a complete loss of HBsAg two weeks after the end of the treatment. Furthermore, none of the cases followed for up to 9 months had any symptoms of HBsAg. The authors postulated that PN may inhibit proliferation of the virus by inhibiting replication of the genetic material of the virus.

The extremely impressive anit-viral properties of PN are demonstrated in another clinical trial involving 160 children (age 1-12 years) with infective hepatitis. The authors reported that the virus was "cured" in 101 of the children, with the other 59 being dropouts. Normal appetite was seen in 7 days, while jaundice, hepatic tenderness, and other symptoms of hepatitis B all disappeared completely within 5 weeks.

Hepatitis B is not the only virus that can potentially be treated by PN. Recent studies have indicated that PN may also be beneficial in the treatment of Human Immunodeficiency Virus (HIV). Studies have shown that PN extract is able to inhibit replication of the HIV virus by inhibiting certain enzymes (such as HIV type-1 reverse transcriptase) essential for replication of the virus. Other evidence suggests that the HIV inhibiting ability of PN extract is related to its alkaloid components.

Liver Protection
In addition to protecting the liver from viruses like hepatitis B, PN has also been documented to protect the liver from damage by a variety of chemical liver toxins. Furthermore, a protein component of PN has been shown to protect liver tissues from oxidative stress in mice.

Kidney stones and Gallstones
Another well documented application of PN extract is for the treatment of kidney and gall stones. Kidney stones are one of the most painful and common urinary tract problems, and it is reported that over 600, 000 patients are treated for gallstones in the U.S. alone each year. In South America, PN is commonly known as "Chanca Piedre" which in the local dialect of Spanish means, "to break stone". The ability of PN extract to inhibit the growth of kidney stones has been clearly demonstrated in both animals and humans. PN has been used to treat gall bladder infections in South America, and is often taken in the form of tea. PN has also been used in Germany and France to treat gall bladder and kidney stones with over a 95% success rate within 1-2 weeks of treatment. A study examining calcium excretion in 69 individuals with past incidences of kidney stones has shown that PN extract significantly decreases calcium levels in the urine. Furthermore, PN has been demonstrated to effectively inhibit the internalization of calcium oxalate crystals, which are the building blocks of kidney stones. Yet another study found that treatment with PN following shock wave therapy for kidney stones improved the outcome of the treatment. A greater proportion of patients taking PN were found to be stone free following treatment, and were less likely to require additional shock wave therapy.

In addition to its ability to inhibit crystal internalization, PN's ability to treat kidney stones may be further enhanced by the powerful spasmolytic, or muscle relaxant, activity of one of the constituents of PN, phyllanthin. Relaxation of the smooth muscle of the kidney tubules and ureter may help to expel stones.

Malaria
Although it has yet to be tested in humans, in vitro and in vivo studies with mice have indicated that PN shows potential as an anti-malaria agent. In vitro studies have shown that PN extracts are capable of inhibiting growth of the parasite causing malaria by 50-100%. Furthermore, when mice were given doses of 500mg/kg of PN extracts over the course of 4 days the incidence of parasitic infection was suppressed by up to 73%.

In Conclusion
Extracts of PN have a wide variety of therapeutic applications. Results of animal studies and human clinical trials have provided compelling evidence of PN's effectiveness in the treatment of hepatitis B and kidney stones. Other beneficial effects of PN are still being investigated, but the potential of its use in the treatment of HIV, Malaria, and other disorders such as diabetes and hypertension are promising. 

References

Bagalkotkar G, Sagineedu SR, Saad MS, Stanslas J. "Phytochemicals from Phyllanthis niuri Linn. And their pharmacological properties: a review." Journal of Pharmacy and Pharmacology 2006; 58: 1559-70.

Calixto JB, Santos ARS, Filho VC, Yunes RS. "A Review of the plants of the genus Phyllanthus: their chemistry, pharmacology and therapeutic potential." Medicinal Research Reviews 1998; 18(4): 225-58.

Campos AH, Schor N. "Phyllanthus niruri inhibits calcium oxalate endocytosis by renal tubular cells: its role in urolithiasis." Nephron 1999; 81(4): 393-7.

Campos AH, Schor N. "Phyllanthus niruri inhibits calcium oxalate endocytosis by renal tubular cells: its role in urolithiasis." Nephron 1999; 81(4): 393-7.

Freitas AM, Schor N, Boim MA. "The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation." BJU Int 2002 Jun; 89(9): 829-34.

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

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." Journal of Urology 2006; 176(3):1020-2.

Naik AD, Juvekar AR. Effects of alkaloidal extract of Phyllanthus niruri on HIV replication." Indian Journal of Medical Science; 57(9): 387-93

Ogata T, Higuchi H, Mochida S, Matsumoto H, Kato A, Endo T, Kaji A, Kaji H. "HIV-1 reverse transcriptase inhibitor from Phyllanthus niruri." AIDS Res Hum Retroviruses 1992 Nov; 8(11): 1937-44.

Syamasundar KV, Singh B, Thakur RS, Husain A, Kiso Y, Hikino H. "Antihepatotoxic principles of Phyllanthus niruri herbs." J Ethnopharmacol 1985 Sep; 14(1): 41-4.

Phytochemicals from Phyllanthus niruri Linn. and their pharmacological properties: a review
J Pharm Pharmacol. 2006 Dec;58(12):1559-70
Bagalkotkar G, Sagineedu SR, Saad MS, Stanslas J..

This review discusses the medicinal plant Phyllanthus niruri Linn. (Euphorbiaceae), its wide variety of phytochemicals and their pharmacological properties. The active phytochemicals, flavonoids, alkaloids, terpenoids, lignans, polyphenols, tannins, coumarins and saponins, have been identified from various parts of P. niruri. Extracts of this herb have been proven to have therapeutic effects in many clinical studies. Some of the most intriguing therapeutic properties include anti-hepatotoxic, anti-lithic, anti-hypertensive, anti-HIV and anti-hepatitis B. Therefore, studies relating to chemical characteristics and structural properties of the bioactive phytochemicals found in P. niruri are very useful for further research on this plant as many of the phytochemicals have shown preclinical therapeutic efficacies for a wide range of human diseases, including HIV/AIDS and hepatitis B.


Effects of alkaloidal extract of Phyllanthus niruri on HIV replication
Indian J Med Sci. 2003 Sep;57(9):387-93
Naik AD, Juvekar AR.

Phyllanthus niruri has been found to exhibit marked inhibitory effect on hepatitis B virus evident by its exhaustive utility in cases of chronic jaundice. However, till date, research has not been focused on identification and validation of active pharmacophores of Phyllanthus niruri responsible for the reported inhibitory effect of its aqueous extract on anti-human immunodeficiency virus. The present investigation examines the anti-HIV effects of the alkaloidal extract of Phyllanthus niruri in human cell lines. The inhibitory effect on HIV replication was monitored in terms of inhibition of virus induced cytopathogenecity in MT-4 cells. The alkaloidal extract of Phyllanthus niruri showed suppressing activity on strains of HIV-1 cells cultured on MT-4 cell lines. The CC50 for the extract was found to be 279.85 microgmL(-1) whereas the EC50 was found to be 20.98 microgmL(-1). Interestingly the Selectivity Index (SI) was found to be 13.34, which showed a clear selective toxicity of the extract for the viral cells. The alkaloidal extract of Phyllanthus niruri was thus found to exhibit sensitive inhibitory response on cytopathic effects induced by both the strains of human immunodeficiency virus on human MT-4 cells in the tested concentrations.


Protein isolate from the herb, Phyllanthus niruri L. (Euphorbiaceae), plays hepatoprotective role against carbon tetrachloride induced liver damage via its antioxidant properties.
Food Chem Toxicol. 2007 May;45(5):817-26. Epub 2006 Nov 11.
Bhattacharjee R, Sil PC.

Phyllanthus niruri L. (Euphorbiaceae) (P. niruri) is a well-known hepatoprotective herbal plant. In the present study, hepatoprotective potential of the protein isolate of P. niruri was investigated against carbon tetrachloride (CCl(4)) induced liver damage in vivo. Protein isolate of P. niruri was intraperitoneally injected in mice either prior to (preventive) or after the induction of toxicity (curative). Levels of different liver marker enzymes in serum and different anti-oxidant enzymes, as well as lipid peroxidation products and glutathione (GSH) in liver homogenates were measured in normal, control (toxicity induced) and protein isolate treated mice. Administration of CCl(4) increased the serum glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) levels of mice sera along with increased lipid peroxidation and reduced levels of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the liver. Treatment with the protein isolate of P. niruri significantly altered these changes to almost normal. The protein isolate also showed protective properties as was evidenced in histopathological studies. Results suggest that the protein isolate of P. niruri protects liver tissues against oxidative damage and somehow helps stimulating repair mechanism present in liver. It could be used as an effective hepatoprotector against CCl(4) induced liver damage.


Hepatoprotection of Phyllanthus maderaspatensis against experimentally induced liver injury in rats.
Fitoterapia. 2007 Feb;78(2):134-41. Epub 2006 Nov 16.
Asha VV, Sheeba MS, Suresh V, Wills PJ.

The hexane extract of Phyllanthus maderaspatensis (200 and 100 mg/kg) showed significant hepatoprotection on carbon tetrachloride and thioacetamide induced liver damage in rats. The protective effect was evident from serum biochemical parameters and histopathological analysis. Rats treated with P. maderaspatensis remarkably prevented the elevation of serum AST, ALT and LDH and liver lipid peroxides in CCl(4) and thioacetamide treated rats. Hepatic glutathione levels significantly increased by the treatment with the extracts. Histopathological changes induced by CCl(4) and thioacetamide were also significantly reduced by the extract treatment. The activity of hexane extracts of P. maderaspatensis was comparable to that of silymarin, the reference hepatoprotective drug. 


The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation.
BJU Int 2002 Jun; 89(9): 829-34.
Freitas AM, Schor N, Boim MA.

Objective: To evaluate the effect of an aqueous extract of Phyllanthus niruri (Pn), a plant used in folk medicine to treat lithiasis, on the urinary excretion of endogenous inhibitors of lithogenesis, citrate, magnesium and glycosaminoglycans (GAGs).
Materials and methods: The effect of chronic (42 days) administration of Pn (1.25 mg/mL/day, orally) was evaluated in a rat model of urolithiasis induced by the introduction of a calcium oxalate (CaOx) seed into the bladder of adult male Wistar rats. The animals were divided into four groups: a sham control (16 rats); a control+Pn (six); CaOx+water instead of Pn (14); and CaOx+Pn (22). Plasma and urine were collected after 42 days of treatment for biochemical analysis and the determination of urinary excretion of citrate, magnesium and GAGs. The animals were then killed and the calculi analysed.
Results: The creatinine clearance or urinary and plasma concentrations of Na+, K+, Ca2+, oxalate, phosphate and uric acid were unaffected by Pn or the induction of lithiasis. Treatment with Pn strongly inhibited the growth of the matrix calculus and reduced the number of stone satellites compared with the group receiving water. The calculi were eliminated or dissolved in some treated animals (three of 22). The urinary excretion of citrate and magnesium was unaffected by Pn treatment. However, the mean (sd) urinary concentration of GAGs was significantly lower in rats treated with CaOx+Pn, at 5.64 (0.86) mg/g creatinine, than when treated with CaOx + water, at 11.78 (2.21) mg/g creatinine. In contrast, the content of GAGs in the calculi was higher in the CaOx + Pn rats, at 48.0 (10.4) g/g calculus, than in the CaOx + water group, at 16.6 (9.6) g/g calculus.
Conclusion: These results show that Pn has an inhibitory effect on crystal growth, which is independent of changes in the urinary excretion of citrate and Mg, but might be related to the higher incorporation of GAGs into the calculi.


Phyllanthus niruri inhibits calcium oxalate endocytosis by renal tubular cells: its role in urolithiasis.
Nephron 1999; 81(4): 393-7.
Campos AH, Schor N.

We investigated the in vitro effect of an aqueous extract of Phyllanthus niruri L. on a model of CaOx crystal endocytosis by Madin-Darby canine kidney cells. The extract exhibited a potent and effective non-concentration-dependent inhibitory effect on the CaOx crystal internalization. This response was present even at very high (pathologic) CaOx concentrations and no P. niruri L.-induced toxic effect could be detected. Biochemical analysis of culture media containing P. niruri L. did not provide any clues for the elucidation of the cellular pathways affected by this natural product. Although further studies are necessary for a better understanding of the role of P. niruri L. in urolithiasis, our findings show that this natural product could be an attractive alternative for the treatment of urinary stones.


HIV-1 reverse transcriptase inhibitor from Phyllanthus niruri.
AIDS Res Hum Retroviruses 1992 Nov; 8(11): 1937-44.
Ogata T, Higuchi H, Mochida S, Matsumoto H, Kato A, Endo T, Kaji A, Kaji H.

An aqueous extract of Phyllanthus niruri (Euphorbiaceae) inhibited human immunodeficiency virus type-1 reverse transcriptase (HIV-1-RT). The inhibitor against HIV-1-RT in this plant was purified by combination of three column chromatographies, Sephadex LH-20, cellulose, and reverse-phase high-performance liquid chromatography. The inhibitor was then identified by nuclear magnetic resonance (NMR) spectra as repandusinic acid A monosodium salt (RA) which was originally isolated from Mallotus repandus. The 50% inhibitory doses (ID50) of RA on HIV-1-RT and DNA polymerase alpha (from HeLa cells) were 0.05 microM and 0.6 microM, respectively, representing approximately a 10-fold more sensitivity of HIV-1-RT compared with DNA polymerase alpha. RA was shown to be a competitive inhibitor with respect to the template-primer while it was a noncompetitive inhibitor with respect to the substrate. RA as low as 10.1 microM inhibited HIV-1-induced cytopathogenicity in MT-4 cells. In addition, 4.5 microM of RA inhibited HIV-1-induced giant cell formation of SUP-T1 approximately 50%. RA (2.5 microM) inhibited up to 90% of HIV-1 specific p24 antigen production in a Clone H9 cell system.


Phyllanthus niruri inhibits calcium oxalate endocytosis by renal tubular cells: its role in urolithiasis.
Nephron 1999; 81(4): 393-7.
Campos AH, Schor N.

We investigated the in vitro effect of an aqueous extract of Phyllanthus niruri L. on a model of CaOx crystal endocytosis by Madin-Darby canine kidney cells. The extract exhibited a potent and effective non-concentration-dependent inhibitory effect on the CaOx crystal internalization. This response was present even at very high (pathologic) CaOx concentrations and no P. niruri L.-induced toxic effect could be detected. Biochemical analysis of culture media containing P. niruri L. did not provide any clues for the elucidation of the cellular pathways affected by this natural product. Although further studies are necessary for a better understanding of the role of P. niruri L. in urolithiasis, our findings show that this natural product could be an attractivealternative for the treatment of urinary stones.


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

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.


Antihepatotoxic principles of Phyllanthus niruri herbs.
J Ethnopharmacol 1985 Sep; 14(1): 41-4.
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.