Cytotoxic, caspase-3 induction and in vivo hepatoprotective effects of phyllanthin, a major constituent of Phyllanthus niruri

The antiproliferative activity of phyllanthin (the major constituent in the decoction of Phyllanthus niruri L.) against human liver carcinoma HepG2 cells, the mechanism of cell death and the protective effect against carbon tetrachloride (CCl4)-induced hepatotoxicity in mice were investigated. Phyllanthin showed dose- and time-dependent growth inhibitions of HepG2 cells with the lowest EC50 value (10.16 ± 0.21 µg/ml) at 72 hours of treatment. Acute exposure to this compound exerted a significant caspase-3 expression that reached its peak after 8 hours of treatment (P < 0.001). Oral pre-treatment of phyllanthin at a dose of 120 mg/kg prior to CCl4-treatment effectively prevented the hepatic damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST). These are the indications that phyllanthin is able to act independently to inhibit HepG2 cell proliferation via apoptotic cell death and to protect from hepatic injuries. Therefore, the effects of P. niruri extracts in the treatment of liver diseases can be related to the presence of phyllanthin.