Effect and mechanism of methyl helicterate isolated from Helicteres angustifolia (Sterculiaceae) on hepatic fibrosis induced by carbon tetrachloride in rats

Ethnopharmacological relevance: Methyl helicterate is a triterpenoid isolated from Helicteres angustifolia (Sterculiaceae), one of the valuable traditional Chinese herbs. Antifibrotic activities of H. angustifolia have been extensively proved. Aim of the study: The purpose of this study was to investigate the effect of methyl helicterate (MH) on liver fibrosis in rats induced by carbon tetrachloride (CCl4) and to explore its underlying mechanism. Materials and methods: Hepatic fibrosis was induced in male Sprague-Dawley (SD) rats by intragastric administration with 2 ml/kg CCl4 (mixed 1:1 in peanut oil) twice a week for 12 weeks. To evaluate the effect of MH (16.72, 33.45, 66.90 mg/kg) on hepatic fibrosis, liver function, histological study and hepatic fibrosis evaluation were performed. Liver function was assessed by determining the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb) and total protein (TP). The biomarkers such as hydroxyproline (Hyp), hyaluronic acid (HA), type III precollagen (PCIII) and laminin (LN) were examined for the evaluation of hepatic fibrosis. The underlying mechanism was investigated by measuring oxidative stress level and detecting the expression of TGF-beta 1 mRNA and Smad3 protein. Results: MH (33.45, 66.90 mg/kg) treatment significantly inhibited the loss of body weight and the increase of liver index in rats induced by CCl4. MH also improved the liver function as indicated by decreasing serum enzymatic activities of ALT, AST, TP and Alb (P < 0.05). Histological results indicated that MH alleviated liver damage and reduced the formation of fibrous septa. Moreover, MH significantly decreased liver Hyp, HA, LN and PCIII (P<0.05). Research on mechanism showed that MH could markedly reduce liver malondialdehyde (MDA) concentration, increase activities of liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and inhibit the expression of TGF-beta 1 mRNA and Smad3 protein (P<0.05). Conclusions: Our findings indicated that MH can inhibit CCl4-induced hepatic fibrosis, which may be ascribed to its radical scavenging action, antioxidant activity, and modulation of TGF-beta-Smad3 signaling pathway. (C) 2012 Elsevier Ireland Ltd. All rights reserved.