Baicalin attenuates diet induced nonalcoholic steatohepatitis by inhibiting inflammation and oxidative stress via suppressing JNK signaling pathways

Nonalcoholic steatohepatitis may develop into hepatic cirrhosis. The therapeutic drugs for NASH are absent. Baicalin (BC) has hepatoprotective effect, while whether BC could prevent the development of NASH is unknown. This study aimed to investigate the effect of BC on the development of diet induced NASH and the possible mechanisms involved. Mice were fed with high fat and high cholesterol (HFC) diet to establish a NASH model, BC (0.5% w/w) was added into the diet to evaluate its effect on NASH. Mice fed an HFC diet developed NASH in 12 weeks. BC administration attenuated hepatic steatosis, inflammation and fibrosis induced by HFC diet. The NALFD activity score (NAS) was sharply decreased by BC. Mice serum ALT and AST were decreased in the BC group. BC decreased hepatic inflammatory cell infiltration, inflammatory genes (MCP-1, TNF alpha) and fibrosis genes (COL1, alpha-SMA, TGF beta) mRNA expression. BC has antioxidant function evidenced by upregulated hepatic GSH and SOD levels and downregulated MDA levels. BC restored some oxidative stress markers including 4-HNE, 8-OHdG in liver. Western blot analysis stated that BC suppressed pro-inflammatory COX-2 levels, pro-oxidative CYP2E1 levels and phosphorylation of JNK in mice liver. Collectively, BC can attenuate diet induced NASH and the mechanism in which possibly due to its anti-inflammatory and anti-oxidant effects via blockade of the activation of JNK.