Inhibitory effects of salvianolic acid B on CCl4-induced hepatic fibrosis through regulating NF-κB/IκBα signaling

Ethnopharmacological relevance: Hepatic fibrosis, a precursor of liver cirrhosis, is a consequence of severe liver damage that occurs in many patients with chronic liver diseases. Salvianolic acid B (SA-B) is one of water soluble compounds derived from Salvia miltiorrhiza Bunge (Danshen in Chinese) widely used for chronic liver diseases. In this study we investigated the protective effects of SA-B on CCl4-induced hepatic fibrosis. Materials and methods: Hepatic fibrosis in rats was induced by carbon tetrachloride (CCl4). Rats were divided into four groups, including normal controls (N group), model (M group), low SA-B of 10 mg/kg body weight (L group), or high SA-B of 20 mg/kg body weight (H group). After 6 weeks, macroscopic features of the liver and weight ratio of liver to body were measured. Liver fibrosis of the rats was evaluated by HE and Massion staining. Activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were checked with automated biochemistry analyzer. Serum levels of hyaluronic acid (HA), type IV collagen (IV-C), Laminin (LN) and procollagen III peptide (PIIIP) were detected by radioimmunoassay (RIA). The expression of NF-kappa B and I kappa B alpha was detected by western blotting. Results: SA-B was shown to reduce CCl4-induced hepatic fibrosis in rats. The serum levels of ALT, AST, and TBIL were significantly lower in the SA-B treatment groups than in the M group. Compared the M group, the serum levels of HA, LN, IV-C and PULP were decreased markedly after treatment with SA-B, especially in the H group. Treatment with SA-B at 10-20 mg/kg (L and N groups, respectively) dose-dependently decreased the expression of NF-kappa B in the nucleolus and increased the expression levels of NF-kappa B and ham protein in the cytoplasm compared to that of the M group. Conclusions: This study reveals that SA-B could prevent the progression of liver angiogenesis and alleviate liver fibrosis possibly by regulating the expression of NF-kappa B and I kappa B alpha. Crown Copyright (C) 2012 Published by Elsevier Ireland Ltd. All rights reserved.