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Title: Quercetin improves hepatic fibrosis reducing hepatic stellate cells and regulating pro-fibrogenic/anti-fibrogenic molecules balance
Author: Hernandez-Ortega, L.D.
Alcantar-Diaz, B.E.
Ruiz-Corro, L.A.
Sandoval-Rodriguez, A.
Bueno-Topete, M.
Armendariz-Borunda, J.
Salazar-Montes, A.M.
Issue Date: 2012
Abstract: Background and Aim: 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 CCl4 for 8 weeks and concomitantly treated with 100mg/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. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
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