Antifibrotic activity of Phyllanthus maderaspatensis L. in Wistar rats

This study evaluates the effectiveness of Phyllanthus maderaspatensis L. against liver fibrosis in Wistar rats. Hepatic fibrosis was experimentally induced in male rats with CCl4 administration. Animals were then post treated with 200 mg/kg dose of P. maderaspatensis hexane extract (PmHE). Fibrosis was studied using biochemical assays and histopathological techniques. The molecular mechanism of reversion of hepatic fibrosis by PmHE was studied, using semiquantitative RT-PCR, western blotting and gelatine zymography. PmHE was analyzed using high performance liquid chromatography (HPLC) and high performance thin layer chromatography (HPTLC). PmHE was subjected to toxicity evaluation in rats. Post treatment with PmHE almost normalized CCl4 induced fibrotic changes. PmHE treatment normalized serum parameters, reduced lipid peroxidation and maintained the normal level of reduced glutathione pool. The increased levels of alpha-smooth muscle actin (SMA), collagen I and collagen III and mRNA transcripts were effectively reversed with PmHE post treatment. Histopathology of the liver confirmed its recovery from hepatic fibrosis. Moreover, the post treatment with PmHE, showed a significant reduction in the hydroxyproline level in the liver. Further, matrix metalloproteinase (MMP) activity of MMP-9 and MMP-2 was also reduced. HPTLC and HPLC analysis showed the presence of phyllanthin and quercetin in the extract. The mechanism of action of PmHE against hepatic fibrosis could be at least partly, due to the inhibition of oxidative stress. PmHE was found to be safe, based on the toxicity evaluation. Therefore, PmHE is a very promising antifibrotic agent.