Antifibrotic effects of chronic baicalein administration in a CCl4 liver fibrosis model in rats

Baicalein was a major bioactive flavonoid derived from Radix Scutellariae in Xiao-Chai-Hu-Tang which was commonly used to treat chronic hepatitis and liver fibrosis in China. The aim of this study was to assess whether chronic baicalein administration could prevent liver fibrosis induced by carbon tetrachloride (CCl(4)) in rats and investigate its possible protective mechanism. The antifibrotic effects of baicalein were assessed directly by hepatic histology and indirectly by measuring levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), hepatic hyaluronic acid, laminin and procollagen type III (PCIII) in serum, as well as hydroxyproline and matrix metalloproteinases (MMPs) in liver. In addition, we further investigated protein synthesis of platelet derived growth factor (PDGF) beta receptor which has been identified as attractive target for therapeutic intervention. CCl(4) treatment increased levels of AST, ALT, hyaluronic acid, laminin, and PCIII in serum, as well as hydroxyproline and MMPs in liver. Baicalein treatment (20, 40, or 80 mg/kg for 10 weeks) dose-dependently decreased levels of these markers. Baicalein also reduced inflammation, destruction of liver architecture, and collagen accumulation and significantly inhibited protein synthesis of PDGF-beta receptor. Together, our results suggest that chronic baicalein administration inhibits stellate cell activation and proliferation by the down-regulation of PDGF-beta receptor and prevents the development of CCl(4) induced liver fibrosis in rats.