Ferulic acid protects against carbon tetrachloride-induced liver injury in mice

Abstract

Ferulic acid (FA), isolated from the root of Scrophularia buergeriana, is a phenolic compound possessing antioxidant, anticancer, and antiinflammatory activities. Here, we have investigated the hepatoprotective effect of FA against carbon tetrachloride (CCl 4)-induced acute liver injury. Mice were treated intraperitoneally with vehicle or FA (20, 40, and 80 mg/kg) 1 h before and 2 h after CCl 4 (20 μl/kg) injection. The serum activities of aminotransferases and the hepatic level of malondialdehyde were significantly higher after CCl 4 treatment, while the concentration of reduced glutathione was lower. These changes were attenuated by FA. The serum level and mRNA expression of tumor necrosis factor-α significantly increased after CCl 4 treatment, and FA attenuated these increases. The levels of inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expression after CCl 4 treatment were significantly higher and FA reduced these increases. CCl 4-treated mice showed increased nuclear translocation of nuclear factor-κB (NF-κB), and decreased levels of inhibitors of NF-κB in cytosol. Also, CCl 4 significantly increased the level of phosphorylated JNK and p38 mitogen-activated protein (MAP) kinase, and nuclear translocation of activated c-Jun. FA significantly attenuated these changes. We also found that acute CCl 4 challenge induced TLR4, TLR2, and TLR9 protein and mRNA expression, and FA significantly inhibited TLR4 expression. These results suggest that FA protects from CCl 4-induced acute liver injury through reduction of oxidative damage and inflammatory signaling pathways.