title: Emodin protects rat liver from CCl(4)-induced fibrogenesis via inhibition of hepatic stellate cells activation.
abstract: OBJECTIVE
  To investigate the role of emodin in protecting the liver against fibrogenesis caused by carbon tetrachloride (CCl(4)) in rats and to further explore the underlying mechanisms.
  
  
  METHODS
  Rat models of experimental hepatic fibrosis were established by injection with CCl(4); the treated rats received emodin via oral administration at a dosage of 20 mg/kg twice a week at the same time. Rats injected with olive oil served as a normal group. Histopathological changes were observed by hematoxylin and eosin staining. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and hepatic hydroxyproline content were assayed by biochemical analyses. The mRNA and protein relevant to hepatic stellate cell (HSC) activation in the liver were assessed using real-time reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, western blotting and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The degree of hepatic fibrosis increased markedly in the CCl(4) group compared to the normal group (P < 0.01), and decreased markedly in the emodin group compared to the CCl(4) group according to METAVIR scale (P < 0.01) compared with those in the normal control group (51.02 +/- 10.64 IU/L and 132.28 +/- 18.14 IU/L). The activities of serum ALT and AST were significantly higher in rats injected with CCl(4) (289.25 +/- 68.84 IU/L and 423.89 +/- 35.67 IU/L, both P < 0.05). The activities of serum ALT and AST were significantly reduced by administration of emodin (176.34 +/- 47.29 IU/L and 226.1 +/- 44.52 IU/L, both P < 0.05). Compared with the normal controls (54.53 +/- 13.46 mg/g), hepatic hydroxyproline content was significantly higher in rats injected with CCl(4) (120.27 +/- 28.47 mg/g, P < 0.05). Hepatic hydroxyproline content was significantly reduced in the rats treated with emodin at 20 mg/kg (71.25 +/- 17.02 mg/g, P < 0.05). Emodin significantly protected the liver from injury by reducing serum AST and ALT activities and reducing hepatic hydroxyproline content. The mRNA levels of transforming growth factor-beta1 (TGF-beta1), Smad4 and alpha-SMA in liver tissues were significantly down-regulated in SD rats that received emodin treatment. Furthermore, significant down-regulation of serum TGF-beta1 protein levels and protein expression of Smad4 and alpha-SMA in liver tissues was also observed in the rats. Emodin inhibited HSC activation by reducing the abundance of TGF-beta1 and Smad4.
  
  
  CONCLUSIONS
  Emodin protects the rat liver from CCl(4)-induced fibrogenesis by inhibiting HSC activation. Emodin might be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis.
authors.affiliation: The Institute of Medicine, Qiqihar Medical University, JianHua District, Qiqihar, Heilongjiang Province, China.
authors.forename: Miao-Xian
authors.initials: MX
authors.lastname: Dong
authors.forename: Yan
authors.initials: Y
authors.lastname: Jia
authors.forename: Ying-Bo
authors.initials: YB
authors.lastname: Zhang
authors.forename: Cheng-Chong
authors.initials: CC
authors.lastname: Li
authors.forename: Yu-Tao
authors.initials: YT
authors.lastname: Geng
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: Li
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Liu
authors.forename: Ying-Cai
authors.initials: YC
authors.lastname: Niu
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004195:Disease Models, Animal; D004642:Emodin / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism*; D006909:Hydroxyproline / Q000737:chemistry; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D000069463:Olive Oil; D010938:Plant Oils / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000069463:Olive Oil; D010938:Plant Oils; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D004642:Emodin; D006909:Hydroxyproline