title: Alisol A 24-Acetate Prevents Hepatic Steatosis and Metabolic Disorders in HepG2 Cells.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders including hepatic lipid accumulation and inflammation. Alisol A 24-acetate, a triterpene from Alismatis rhizome, has multiple biologic activities such as hypolipidemic, anti-inflammatory and anti-diabetic. Thus we hypothesized that Alisol A 24 -acetate would have effect on NAFLD. The present study was conducted to investigate the therapeutic effects and potential mechanisms of Alisol A 24-acetate against hepatic steatosis in a free fatty acids (FFAs) induced NAFLD cell model.
  
  
  METHODS
  This study was divided into four groups including Control group, Model group (FFA group), Alisol A 24-acetate (FFA+A) group, Fenofibrate (FFA+F) group. Preventive role of Alisol A 24-acetate was evaluated using 10µM Alisol A 24-acetate plus 1 mM FFA (oleate:palmitate=2:1) incubated with HepG2 cells for 24 h, which was determined by Oil Red O Staining, Oil Red O based colorimetric assay and intracellular triglyceride (TG) content. Besides, the inflammatory cytokines tumor necrosis factor (TNF)- α, interleukin (IL)-6 levels as well as the protein and mRNA expressions that were involved in fatty acid synthesis and oxidation including Adiponectin, AMP-activated protein kinase (AMPK) α, peroxisome proliferator-activated receptor (PPAR) α, sterol regulatory element binding protein 1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1) and acyl coenzyme A oxidase 1 (ACOX1) were detected.
  
  
  RESULTS
  Alisol A 24-acetate significantly decreased the numbers of lipid droplets, Oil Red O lipid content, and intracellular TG content. Besides, inflammatory cytokines TNF-α, IL-6 levels were markedly inhibited by Alisol A 24-acetate. Furthermore, Alisol A 24-acetate effectively increased the protein and mRNA expressions of Adiponectin, the phosphorylation of AMPKα, CPT1 and ACOX1, whereas decreased SREBP-1c, the phosphorylation of ACC and FAS at both protein and mRNA levels. However, there was no significant effect on the protein and mRNA expressions of PPARα by Alisol A 24-acetate.
  
  
  CONCLUSIONS
  These results demonstrated that Alisol A 24-acetate effectively ameliorated hepatic steatosis likely through Adiponectin, which activated AMPKα signaling pathways via down-regulating SREBP-1c, ACC, FAS and up-regulating CPT1 and ACOX1, and inhibited inflammation. Thereby, Alisol A 24-acetate could be a promising candidate for the treatment of NAFLD.
authors.affiliation: Department of Pharmacy, Ganzhou People's Hospital, Nanchang University, Jiangxi, Ganzhou, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zeng
authors.forename: WaiJiao
authors.initials: W
authors.lastname: Tang
authors.forename: JinJin
authors.initials: J
authors.lastname: Yin
authors.forename: LiJuan
authors.initials: L
authors.lastname: Feng
authors.forename: Yabing
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Yao
authors.forename: BenJie
authors.initials: B
authors.lastname: Zhou
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002783:Cholestenones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000378:metabolism; D005227:Fatty Acids; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects; D008659:Metabolic Diseases / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D002783:Cholestenones; D016207:Cytokines; D005227:Fatty Acids; D047493:PPAR alpha; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; C457233:alisol A 24-acetate; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase