title: Ameliorative effects of tannic acid on carbon tetrachloride-induced liver fibrosis in vivo and in vitro.
abstract: We investigated the ameliorative effects and potential mechanisms of tannic acid (TA) in carbon tetrachloride (CCl4)-intoxicated mice and hepatic stellate cells (HSCs). Liver fibrosis was observed in CCl4 (800 ml/kg)-induced mice, and high viability was observed in CCl4 (10 mM)-intoxicated HSCs. Pre-treatment of mice with TA (25 or 50 g/kg/day) significantly ameliorated hepatic morphology and coefficient values and reduced the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), the concentrations of malondialdehyde (MDA) and serum levels of endothelin-1 (ET-1). In addition, TA increased the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and endothelial nitric oxide synthase (eNOS) and the serum level of NO. Moreover, TA reduced the expression of angiotensin II receptor-1 (ATR-1), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), caspase-3, c-fos, c-jun, the ratio of Bax/bcl-2, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TA increased matrix metal proteinase-9 (MMP-9), matrix metalloproteinase-1 (MMP-1). Furthermore, TA (0.01 μM, 0.1 μM or 1 μM) decreased the TIMP-1/MMP-1 ratio and reduced the viability of HSCs. These results indicated that TA exerts significant liver-protective effects in mice with CCl4-induced liver fibrosis. The potential mechanism may rely on the inhibition of collagen accumulation, oxidative stress, inflammation and apoptosis.
authors.affiliation: Department of Pharmacy, The Fourth Hospital of Hebei Medical University, No. 12, Jiankang Road, Shijiazhuang, 050011, Hebei, China. Electronic address: chux2014@126.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Chu
authors.affiliation: Hebei Medical University, No. 361, East Zhongshan Road, Shijiazhuang, 050017, Hebei, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Respiration, The Third Hospital of Shijiazhuang, No. 15, South Sports Street, Shijiazhuang, 050011, Hebei, China.
authors.forename: Yan-min
authors.initials: YM
authors.lastname: Jiang
authors.affiliation: Hebei University of Chinese Medicine, No. 3, Xingyuan Road, Shijiazhuang, 050200, Hebei, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, China.
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, No. 1, Shennong Road of the Central Door, Nanjing, 210038, Jiangsu, China.
authors.forename: Yi-fan
authors.initials: YF
authors.lastname: Bao
authors.affiliation: Hebei University of Chinese Medicine, No. 3, Xingyuan Road, Shijiazhuang, 050200, Hebei, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Hebei University of Chinese Medicine, No. 3, Xingyuan Road, Shijiazhuang, 050200, Hebei, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, China.
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Zhang
authors.affiliation: Hebei University of Chinese Medicine, No. 3, Xingyuan Road, Shijiazhuang, 050200, Hebei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Hebei University of Chinese Medicine, No. 3, Xingyuan Road, Shijiazhuang, 050200, Hebei, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Chest Hospital of Hebei, No. 372, North Shengli Street, Shijiazhuang, 050041, Hebei, China.
authors.forename: Yan-chao
authors.initials: YC
authors.lastname: Luan
authors.affiliation: Intensive Care Unit, Air Force General Hospital, No. 30, Fucheng Road, Haidian, 100142, Beijing, China.
authors.forename: Yong-sheng
authors.initials: YS
authors.lastname: Dong
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000494:pharmacology / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013634:Tannins / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D013634:Tannins; D003094:Collagen; D002251:Carbon Tetrachloride; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1
keywords: Anti-Apoptosis; Anti-Inflammation; Anti-fibrosis; Anti-oxidation; Tannic acid