title: Beneficial effect of quercetin on cholestatic liver injury.
abstract: Bile duct obstruction and subsequent cholestasis are associated with hepatocellular injury, cholangiocyte proliferation, stellate cell activation, Kupffer cell activation, oxidative stress, inflammation and fibrosis. Flavonoids have been shown to confer beneficial health effects, including hepatoprotection. However, the molecular mechanism of flavonoid-mediated hepatoprotection is incompletely understood. In this study, we report the protective effect of quercetin on cholestatic liver injury. Cholestasis was produced by bile duct ligation (BDL) in male Sprague-Dawley rats for 3 weeks. Daily oral administration of quercetin was started 1 week before injury and lasted for 4 weeks. In comparison with the control group, the BDL group showed liver injury, as evidenced by histological changes, and elevation in serum biochemicals, ductular reaction, fibrosis, inflammation and oxidative stress. These pathophysiological changes were attenuated by daily quercetin supplementation. Quercetin alleviated BDL-induced transforming growth factor beta-1 (TGF-β1), interleukin-1 beta, connective tissue growth factor and collagen expression. The antifibrotic effect of quercetin was accompanied by reductions in α-smooth muscle actin-positive matrix-producing cells and Smad 2/3 activity critical to the fibrogenic potential of TGF-β1. Quercetin also attenuated BDL-induced oxidative stress, leukocyte accumulation, nuclear factor (NF)-κB activation and proinflammatory cytokine production. Further studies demonstrated an inhibitory effect of quercetin on MyD88 and TGF-β-activated kinase-1 critical for linking toll-like receptor (TLR) and NF-κB. Taken together, the hepatoprotective, anti-inflammatory and antifibrotic effects of quercetin seem to be multifactorial. The beneficial effects of daily quercetin supplementation are associated with antioxidative and anti-inflammatory potential as well as down-regulation of NF-κB and TGF-β/Smad signaling, probably via interference with TLR signaling.
authors.affiliation: Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung 407, Taiwan; School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Shih-Yi
authors.initials: SY
authors.lastname: Lin
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei 112, Taiwan; Division of Family Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan.
authors.forename: Ya-Yu
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung 407, Taiwan.
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Chuang
authors.affiliation: Department of Pediatrics, Tungs' Taichung MetroHarbor Hospital, Taichung 435, Taiwan.
authors.forename: Pin-Ho
authors.initials: PH
authors.lastname: Pan
authors.affiliation: Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan; Center for General Education, Tunghai University, Taichung 407, Taiwan; Department of Nursing, HungKuang University, Taichung 433, Taiwan. Electronic address: cjchen@vghtc.gov.tw.
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D002779:Cholestasis / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D017931:DNA Primers; D008107:Liver Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D011794:Quercetin / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D011794:Quercetin
keywords: Cholestasis; Fibrosis; Inflammation; Oxidative stress; Quercetin