title: Epigallocatechin gallate attenuated non-alcoholic steatohepatitis induced by methionine- and choline-deficient diet.
abstract: Nonalcoholic fatty liver disease (NAFLD) and its progressive form, nonalcoholic steatohepatitis (NASH), are the most common causes of chronic liver disease. In this study, we evaluated the effects of Epigallocatechin gallate (EGCG) on methionine- and choline-deficient (MCD) diet-induced NASH. Our data showed that EGCG significantly prevented MCD diet-induced liver and body weight loss. Histological analysis showed that EGCG inhibited MCD diet-induced steatohepatitis including fat accumulation and inflammatory cells infiltration. Biochemical analysis data showed that EGCG significantly reduced the elevation of plasma ALT and AST levels but increased plasma triglyceride and cholesterol contents. However, EGCG significantly inhibited hepatic triglyceride and cholesterol content in MCD diet fed mice. Consistent with histology results, EGCG treatment significantly inhibited MCD diet-induced IL-1β, IL-6, TNF-α and MCP-1 mRNA expression. As an antioxidant, EGCG treatment significant inhibited hepatic MDA contents and increased hepatic SOD contents. In addition, transforming growth factor (TGF)-β, collagen I-α1, tissue inhibitor of metalloproteinase 1 (TIMP-1) and α-smooth muscle actin (SMA) mRNA expression, which are markers of hepatic fibrosis, were markedly inhibited by EGCG treatment. Western blot data showed that EGCG inhibited Smad2 and Smad3 phosphorylation in the liver and LX-2 cells which were involved in TGF-β-induced pathway. Taken together, EGCG attenuated NASH induced by MCD diet associated with ameliorating fibrosis, oxidative stress, and hepatic inflammation. Our results indicate that EGCG has beneficial roles in the development of MCD diet-induced NASH.
authors.affiliation: Department of Geriatrics, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Geriatrics, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Geriatrics, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Yuning
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Geriatrics, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Geriatrics, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China. Electronic address: keqiandr@163.com.
authors.forename: Ke
authors.initials: K
authors.lastname: Qian
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002796:Choline Deficiency / Q000150:complications*; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008715:Methionine / Q000172:deficiency*; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D018836:Inflammation Mediators; D008055:Lipids; D016212:Transforming Growth Factor beta; D002392:Catechin; D008715:Methionine; C045651:epigallocatechin gallate
keywords: EGCG; Fibrosis; Inflammation; Nonalcoholic steatohepatitis; Oxidative stress; TGF-β