Mechanism investigation of dioscin against CCl4-induced acute liver damage in mice

The mechanisms of the ameliorating effects of dioscin against CCl4 induced acute liver damage are investigated in this study. Dioscin significantly inhibited (p < 0.01) the increases of serum ALT and AST activities compared with the CCl4-treated animals. The hepatic lipid peroxidation formation and, concentrations of TNF-α and IL-6 were also decreased. Liver histopathologic studies and a DNA laddering assay indicated that dioscin protected hepatocytes against CCl4-induced apoptosis and necrosis. Furthermore, dioscin decreased the protein expressions of Fas/FasL, increased Bcl-2/Bax ratio, inhibited the release of cytochrome c from mitochondrion to cytosol and attenuated CCl4-induced caspase-3 and -8 activities. The expressions of ICAM-1, vimentin, prohibitin, HGF, c-MET and GSTA1 were also regulated by dioscin and iNOS was also involved in the effects of this agent. These protective effects against CCl4 induced acute liver damage might be through inhibiting lipid peroxidation, inflammatory cytokines, necrosis and apoptosis, and dioscin shows promise for development toward the treatment of acute chemically mediated liver injury.

► The mechanisms of dioscin against CCl4 induced acute liver damage are investigated. ► Dioscin inhibited lipid peroxidation, inflammatory cytokines, necrosis and apoptosis. ► Our results are benefit for exploitation of new drug to treat liver damage in future.