J Ethnopharmacol 2000 Nov 1;73(1-2):215-219

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

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.

J Ethnopharmacol 2000 Sep 1;72(1-2):229-238

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

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.

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

Treatment of chronic liver diseases with traditional Chinese medicine.

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.

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

A trial of Phyllanthus amarus in acute viral hepatitis.

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.

Nephron 1999;81(4):393-7

Phyllanthus niruri inhibits calcium oxalate endocytosis by renal tubular cells: its role in urolithiasis.

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.

Planta Med 1999 Feb;65(1):43-6

Antiviral tannins from two Phyllanthus species.

Seven ellagitannins isolated from Phyllanthus myrtifolius and P. urinaria (Euphorbiaceae) have been shown, for the first time, to be active against Epstein-Barr virus DNA polymerase (EBV-DP) at the microM level. All these compounds have the same moiety of a corilagin, and differ from each other by different substitutions at C-2 and C-4 of the glucose core. SAR analysis and molecular modeling reveal that the essential pharmacophore of these tannins resides in the corilagin moiety. The outer complex carboxylic acid moieties appear to act only as auxopharmacore.

Med Res Rev 1998 Jul;18(4):225-58

A review of the plants of the genus Phyllanthus: their chemistry, pharmacology, and therapeutic potential.

The plants of the genus Phyllanthus (Euphorbiaceae) 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. In recent years, the interest in the plants has increased considerably. Substantial progress on their chemistal and pharmacological properties, as well as 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. However, well-controlled, double-binding clinical trials are lacking. 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 the plants belonging to the genus Phyllanthus have potential beneficial therapeutic actions in the management of hepatitis B, nefrolitiase, and in painful disorders.

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.

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.

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

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

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.