Beneficial effect of quercetin on cholestatic liver injury |
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| Institution: | 1. Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung 407, Taiwan;2. School of Medicine, National Yang-Ming University, Taipei 112, Taiwan;3. Division of Family Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan;4. Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan;5. Department of Pediatrics, Tungs’ Taichung MetroHarbor Hospital, Taichung 435, Taiwan;6. Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan;7. Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan;8. Center for General Education, Tunghai University, Taichung 407, Taiwan;9. Department of Nursing, HungKuang University, Taichung 433, Taiwan;1. Department of Biosciences, University of Helsinki, FI-00014 Helsinki, Finland;2. Department of Information and Computer Science, School of Science, Aalto University, FI-00076 Espoo, Finland;3. Meilahti Clinical Proteomics Core Facility, Biochemistry and Developmental Biology, Institute of Biomedicine, University of Helsinki, FI-00014 Helsinki, Finland;4. Folkhälsan Institute of Genetics, University of Helsinki, FI-00014 Helsinki, Finland;1. Laboratory of Physiology, Physiopathology and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe, University Abou-Bekr Belkaïd, Tlemcen 13000, Algeria;2. Department of Technical Sciences, Faculty of Engineering, University Abou-Bekr Belkaïd, Tlemcen 13000, Algeria;3. Laboratory of Bioorganic and Medicinal Chemistry, UMR 7509 CNRS — University of Strasbourg, ECPM, 25 rue Becquerel Street, 67087 Strasbourg, Cedex 2, France;1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafr El-Sheikh University, Egypt;3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azher University, Egypt;4. Department of Pharmacology, College of Pharmacy, Al Jouf University, Saudi Arabia;5. Department of Pharmacology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef 62514, Egypt |
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| 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. |
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