title: Inhibition by curcumin of multiple sites of the transforming growth factor-beta1 signalling pathway ameliorates the progression of liver fibrosis induced by carbon tetrachloride in rats.
abstract: BACKGROUND
  At present there is no effective and accepted therapy for hepatic fibrosis. Transforming growth factor (TGF)-β1 signaling pathway contributes greatly to hepatic fibrosis. Reducing TGF-β synthesis or inhibiting components of its complex signaling pathway represent important therapeutic targets. The aim of the study was to investigate the effect of curcumin on liver fibrosis and whether curcumin attenuates the TGF-β1 signaling pathway.
  
  
  METHODS
  Sprague-Dawley rat was induced liver fibrosis by carbon tetrachloride (CCl4) for six weeks together with or without curcumin, and hepatic histopathology and collagen content were employed to quantify liver necro-inflammation and fibrosis. Moreover, the mRNA and protein expression levels of TGF-β1, Smad2, phosphorylated Smad2, Smad3, Smad7 and connective tissue growth factor (CTGF) were determined by quantitative real time-PCR, Western blot, or immunohistochemistry.
  
  
  RESULTS
  Rats treated with curcumin improved liver necro-inflammation, and reduced liver fibrosis in association with decreased α-smooth muscle actin expression, and decreased collagen deposition. Furthermore, curcumin significantly attenuated expressions of TGFβ1, Smad2, phosphorylated Smad2, Smad3, and CTGF and induced expression of the Smad7.
  
  
  CONCLUSIONS
  Curcumin significantly attenuated the severity of CCl4-induced liver inflammation and fibrosis through inhibition of TGF-β1/Smad signalling pathway and CTGF expression. These data suggest that curcumin might be an effective antifibrotic drug in the prevention of liver disease progression.
authors.affiliation: Department of Gastroenterology and Hepatology, Zhongshan hospital, Fudan University, 180# Fenglin Road, Shanghai, 200032, People's Republic of China.
authors.forename: Qun-yan
authors.initials: QY
authors.lastname: Yao
authors.forename: Bei-li
authors.initials: BL
authors.lastname: Xu
authors.forename: Ji-yao
authors.initials: JY
authors.lastname: Wang
authors.forename: Hong-chun
authors.initials: HC
authors.lastname: Liu
authors.forename: Shun-cai
authors.initials: SC
authors.lastname: Zhang
authors.forename: Chuan-tao
authors.initials: CT
authors.lastname: Tu
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000009:adverse effects; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000008:administration & dosage*; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010766:Phosphorylation; D010936:Plant Extracts / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D010936:Plant Extracts; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride; D003474:Curcumin