title: Chicoric acid attenuate a nonalcoholic steatohepatitis by inhibiting key regulators of lipid metabolism, fibrosis, oxidation, and inflammation in mice with methionine and choline deficiency.
abstract: Nonalcoholic fatty liver diseases (NAFLD) range histopathologically from hepatic steatosis to steatohepatitis. Chicoric acid has beneficial effects on obesity and liver injury, but its effects on nonalcoholic steatohepatitis (NASH) have not yet been determined. This study examined the effects of Crepidiastrum denticulatum extract (CDE) and its active compound chicoric acid in a mouse model of NASH and fibrosis.
  
  
  
  CDE and chicoric acid were orally administrated to mice fed a methionine- and choline-deficient (MCD) diet. HepG2 and AML-12 cells in MCD medium were incubated with chicoric acid. MCD-fed mice developed the histopathological characteristics of human NASH, including altered regulation of lipid metabolism, inflammation, fibrosis, and oxidation-associated expression, along with augmented lipoperoxidation. Administration of CDE or chicoric acid to MCD-fed mice and HepG2 and AML-12 cells in MCD medium reduced oxidative stress by upregulating antioxidant enzymes and decreased inflammation by inhibiting proinflammatory cytokines and nuclear factor-κB activation. In addition, CDE or chicoric acid reduced fibrosis, apoptosis, and lipogenesis-related gene expression and increased AMP Kinase activation both in vivo and in vitro.
  
  
  
  CDE and chicoric acid may be effective in the treatment of NAFLD and NASH.
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Republic of Korea.|Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology, Gangneung, Republic of Korea.
authors.forename: Myungsuk
authors.initials: M
authors.lastname: Kim
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Republic of Korea.|Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology, Gangneung, Republic of Korea.
authors.forename: GyHye
authors.initials: G
authors.lastname: Yoo
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Republic of Korea.|Department of Biological Chemistry, Korea, University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Randy
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Republic of Korea.|Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology, Gangneung, Republic of Korea.
authors.forename: Hyoung Seok
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Republic of Korea.|Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology, Gangneung, Republic of Korea.
authors.forename: Chu Won
authors.initials: CW
authors.lastname: Nho
mesh_terms: D000818:Animals; D019659:Asteraceae / Q000737:chemistry; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D002796:Choline Deficiency / Q000097:blood*; D004195:Disease Models, Animal; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D050356:Lipid Metabolism / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008715:Methionine / Q000097:blood / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology*
chemical_list: D002109:Caffeic Acids; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D013386:Succinates; D008715:Methionine; C100435:chicoric acid
keywords: Chicoric acid; Crepidiastrum denticulatum; Fibrosis; Inflammation; Lipid metabolism; NASH; Oxidative stress