Hepatoprotective activity of berberine is mediated by inhibition of TNF-α, COX-2, and iNOS expression in CCl4-intoxicated mice

This study investigated the protective effects of isoquinoline alkaloid berberine on the CCl4-induced hepatotoxicity in mice. Berberine was administered as a single dose at 5 and 10 mg/kg intraperitoneally (i.p.), 1 h before CCl4 (10%, v/v in olive oil, 2 ml/kg) injection and mice were euthanized 24 h later. The rise in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in CCl4-intoxicated mice was markedly suppressed by berberine in a concentration-dependent manner. The decrease in hepatic activity of superoxide dismutase (Cu/Zn SOD) and an increase in lipid peroxidation were significantly prevented by berberine. Histopathological changes were reduced and the expression of tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) was markedly attenuated by berberine 10 mg/mg. The results of this study indicate that berberine could be effective in protecting the liver from acute CCl4-induced injury. The hepatoprotective mechanisms of berberine may be related to the free radical scavenging and attenuation of oxidative/nitrosative stress, as well as to the inhibition of inflammatory response in the liver.