Involvement of hepatic peroxisome proliferator-activated receptor α/γ in the therapeutic effect of osthole on high-fat and high-sucrose-induced steatohepatitis in rats

Our previous studies have indicated that osthole may be a dual agonist of peroxisome proliferator-activated receptor (PPAR) alpha/gamma and decrease the hepatic lipid accumulation. But there has been no report about therapeutic effect on steatohepatitis. In the present study, we investigated the action of osthole and its potential mechanisms. The rats with steatohepatitis induced by orally feeding high-fat and high-sucrose emulsion were given osthole 5-20 mg/kg for 4 weeks. The results showed that after treatment with osthole, the serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride (TG), and free fatty acid (FFA) levels, the hepatic TG, FFA, tumor necrosis factor-alpha, monocyte chemotactic protein-1, interleukin-6, and interleukin-8 contents, and the hepatic weight and liver index were lowered, especially in the osthole 20 mg/kg group. The histological evaluation of liver specimens demonstrated that osthole might improve the hepatic steatosis and inflammation. At the same time, osthole treatment increased the hepatic protein expressions of PPAR alpha/gamma and lipoprotein lipase, and decreased the hepatic protein expressions of nuclear factor-kappa B, sterol regulatory element-binding protein-1c, fatty acid synthase, and diacylglycerol acyltransferase. These findings demonstrate that osthole is effective in treating rat steatohepatitis, and the PPAR alpha/gamma may be involved in the osthole-induced modulation of hepatic lipogenic gene expressions and inflammatory cytoldne production. (C) 2014 Elsevier B.V. All rights reserved.