Hepatoprotective effect of fraxin against carbon tetrachloride-induced hepatotoxicity in vitro and in vivo through regulating hepatic antioxidant, inflammation response and the MAPK-NF-κB signaling pathway.

Fraxin, a main active component isolated from Cortex Fraxini, possesses a variety of bioactivities. However, there is a research gap in studies related to the hepatoprotective activity of fraxin against carbon tetrachloride (CCl)-induced liver damage has been rarely studied. Thus, the purpose of this study is to evaluate the protective effect of fraxin against CCl-induced liver damage in mice as well as in HepG2 cells, in addition to further improve the underlying mechanisms of hepatoprotective effect for fraxin. In mice model, pretreatment with fraxin (10, 20 or 40mg/kg) along with CCl significantly alleviated liver damage as indicated by the decreased levels of liver index, liver marker enzymes, lipid peroxidation, inflammatory mediators, increased levels of the antioxidant enzymatic and non-enzymatic defense parameters, and improved hepatic histopathology changes. Further, the results of the in vitro study conducted in HepG2 cells indicated that the CCl-induced changes were significantly ameliorated by pretreatment of fraxin. Moreover, immunohistochemistry staining and western blot assay demonstrated that pretreatment with fraxin can down-regulate CCl-induced protein expression of MAPKs, NF-κB and COX-2. Overall, these studies indicate that fraxin exhibits hepatoprotective effect against CCl-induced liver damage by reducing inflammation response, suppressing oxidative stress and lipid peroxidation and enhancing antioxidant activity. The underlying mechanisms of fraxin in CCl-induced acute liver injury may be due to inhibition of MAPK and NF-κB activation. It is possible for fraxin to be used as a hepatoprotective agent.