title: Inhibitory effects of salvianolic acid B on CCl(4)-induced hepatic fibrosis through regulating NF-κB/IκBα signaling.
abstract: BACKGROUND
  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 CCl(4)-induced hepatic fibrosis.
  
  
  METHODS
  Hepatic fibrosis in rats was induced by carbon tetrachloride (CCl(4)). Rats were divided into four groups, including normal controls (N group), model (M group), low SA-B of 10mg/kg body weight (L group), or high SA-B of 20mg/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-κB and IκBα was detected by western blotting.
  
  
  RESULTS
  SA-B was shown to reduce CCl(4)-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 PIIIP were decreased markedly after treatment with SA-B, especially in the H group. Treatment with SA-B at 10-20mg/kg (L and N groups, respectively) dose-dependently decreased the expression of NF-κB in the nucleolus and increased the expression levels of NF-κB and IκBα 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-κB and IκBα.
authors.affiliation: Department of Pharmacy, NO.3 People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201900, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Yu
authors.forename: Zhu-Ying
authors.initials: ZY
authors.lastname: Guo
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Yong-Fang
authors.initials: YF
authors.lastname: Yuan
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001572:Benzofurans / Q000494:pharmacology / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood; D002251:Carbon Tetrachloride; D024141:Collagen Type IV / Q000097:blood; D006820:Hyaluronic Acid / Q000097:blood; D020672:I-kappa B Proteins / Q000378:metabolism*; D007797:Laminin / Q000097:blood; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027544:Salvia; D053630:Depsides
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D001572:Benzofurans; D001663:Bilirubin; D002251:Carbon Tetrachloride; D024141:Collagen Type IV; D006820:Hyaluronic Acid; D020672:I-kappa B Proteins; D007797:Laminin; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D010446:Peptide Fragments; D011347:Procollagen; D020011:Protective Agents; C000606206:Nfkbia protein, rat; C041876:procollagen Type III-N-terminal peptide; C076944:salvianolic acid B; D053630:Depsides