title: Quercetin improves hepatic fibrosis reducing hepatic stellate cells and regulating pro-fibrogenic/anti-fibrogenic molecules balance.
abstract: OBJECTIVE
  Development of hepatic cirrhosis involves oxidative stress, inflammation, hepatic stellate cells (HSC)s activation and fibrosis. On the other hand, quercetin, a natural flavonoid is a potent antioxidant and activator of superoxide dismutase and catalase. The aim was to determinate the effect of quercetin on HSCs and development of hepatic fibrosis.
  
  
  METHODS
  Wistar male rats were chronically intoxicated with CCl(4) for 8 weeks and concomitantly treated with 100 mg/kg per day of quercetin. Oxidative state, inflammation and fibrosis were evaluated. Effect of quercetin on apoptosis of HSC was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling reaction.
  
  
  RESULTS
  Sixty percent of reduction in fibrosis index was observed with quercetin treatment compared with control animals. Considerable reduction on hepatic enzymes was detected in the quercetin group. Expression of pro-fibrotic genes (transforming growth factor-β [TGF-β], Collagen 1α [Col-1α] and connective tissue growth factor [CTGF]) were decreased by quercetin. Quercetin increased gene expression and functional activity of antioxidant enzymes superoxide dismutase and catalase. Inflammatory index was highly reduced as determined by H-E staining and pro-inflammatory cytokines expression and nuclear factor-κB activation were also inhibited. A significant reduction of 65% on activated HSC number was detected when rats were treated with quercetin. Quercetin also induced activation of matrix metalloproteinases MMP2 and MMP9 contributing to decreased index of fibrosis.
  
  
  CONCLUSIONS
  Treatment with quercetin reduces oxidation and inflammation and also prevents liver fibrosis, through induction of HSC apoptosis and activation of MMPs.
authors.affiliation: Institute of Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, CUCS, University of Guadalajara, Guadalajara, Jalisco.
authors.forename: Luis Daniel
authors.initials: LD
authors.lastname: Hernández-Ortega
authors.forename: Blanca Estela
authors.initials: BE
authors.lastname: Alcántar-Díaz
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Ruiz-Corro
authors.forename: Ana
authors.initials: A
authors.lastname: Sandoval-Rodriguez
authors.forename: Miriam
authors.initials: M
authors.lastname: Bueno-Topete
authors.forename: Juan
authors.initials: J
authors.lastname: Armendariz-Borunda
authors.forename: Adriana María
authors.initials: AM
authors.lastname: Salazar-Montes
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000473:pathology*; D007249:Inflammation / Q000517:prevention & control; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D045726:Metalloproteases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D011794:Quercetin; D045726:Metalloproteases