title: Epigallocatechin gallate attenuates fibrosis, oxidative stress, and inflammation in non-alcoholic fatty liver disease rat model through TGF/SMAD, PI3 K/Akt/FoxO1, and NF-kappa B pathways.
abstract: OBJECTIVE
  To investigate the protective mechanisms of an 85 % pure extract of (-) epigallocatechin gallate (EGCG) in the development of fibrosis, oxidative stress and inflammation in a recently developed dietary-induced animal model of non-alcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  Female Sprague-Dawley rats were fed with either normal rat diet or high-fat diet for 8 weeks to develop NAFLD. For both treatments, rats were treated with or without EGCG (50 mg/kg, i.p. injection, 3 times per week). At the end, blood and liver tissue samples were obtained for histology, molecular, and biochemical analyses.
  
  
  RESULTS
  Non-alcoholic fatty liver disease (NAFLD) rats showed significant amount of fatty infiltration, necrosis, fibrosis, and inflammation. This was accompanied by a significant expressional increase in markers for fibrosis, oxidative stress, and inflammation. TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways were also activated. Treatment with EGCG improved hepatic histology (decreased number of fatty score, necrosis, and inflammatory foci), reduced liver injury (from ~0.5 to ~0.3 of ALT/AST ratio), attenuated hepatic changes including fibrosis (reduction in Sirius Red and synaptophysin-positive stain) with down-regulation in the expressions of key pathological oxidative (e.g. nitrotyrosine formation) and pro-inflammatory markers (e.g. iNOS, COX-2, and TNF-α). EGCG treatment also counteracted the activity of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Treatment with EGCG did not affect the healthy rats.
  
  
  CONCLUSIONS
  Epigallocatechin gallate (EGCG) reduced the severity of liver injury in an experimental model of NAFLD associated with lower concentration of pro-fibrogenic, oxidative stress, and pro-inflammatory mediators partly through modulating the activities of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Therefore, green tea polyphenols and EGCG are useful supplements in the prevention of NAFLD.
authors.affiliation: Center for Gene and Cell Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China, jia.xiao@siat.ac.cn.
authors.forename: Jia
authors.initials: J
authors.lastname: Xiao
authors.forename: Chi Tat
authors.initials: CT
authors.lastname: Ho
authors.forename: Emily C
authors.initials: EC
authors.lastname: Liong
authors.forename: Amin A
authors.initials: AA
authors.lastname: Nanji
authors.forename: Tung Ming
authors.initials: TM
authors.lastname: Leung
authors.forename: Thomas Yue Huen
authors.initials: TY
authors.lastname: Lau
authors.forename: Man Lung
authors.initials: ML
authors.lastname: Fung
authors.forename: George L
authors.initials: GL
authors.lastname: Tipoe
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D059305:Diet, High-Fat; D015536:Down-Regulation; D005234:Fatty Liver / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005355:Fibrosis; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000071161:Forkhead Box Protein O1
chemical_list: D000410:Alanine Transaminase; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D002392:Catechin; D051546:Cyclooxygenase 2; D051858:Forkhead Transcription Factors; D020778:Matrix Metalloproteinase 2; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051785:Smad Proteins; D014409:Tumor Necrosis Factor-alpha; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C045651:epigallocatechin gallate; C496318:Nos2 protein, rat; C489691:Ptgs2 protein, rat; C522363:Mmp2 protein, rat