title: The Mechanism by Which Amentoflavone Improves Insulin Resistance in HepG2 Cells.
abstract: BACKGROUND
  The aim of this study was to explore the mechanism by which amentoflavone (AME) improves insulin resistance in a human hepatocellular liver carcinoma cell line (HepG2).
  
  
  METHODS
  A model of insulin resistant cells was established in HepG2 by treatment with high glucose and insulin. The glucose oxidase method was used to detect the glucose consumption in each group. To determine the mechanism by which AME improves insulin resistance in HepG2 cells, enzyme-linked immunosorbent assay (ELISA) and western blotting were used to detect the expression of phosphatidyl inositol 3-kinase (PI3K), Akt, and pAkt; the activity of the enzymes involved in glucose metabolism; and the levels of inflammatory cytokines.
  
  
  RESULTS
  Insulin resistance was successfully induced in HepG2 cells. After treatment with AME, the glucose consumption increased significantly in HepG2 cells compared with the model group (MG). The expression of PI3K, Akt, and pAkt and the activity of 6-phosphofructokinas (PFK-1), glucokinase (GCK), and pyruvate kinase (PK) increased, while the activity of glycogen synthase kinase-3 (GSK-3), phosphoenolpyruvate carboxylase kinase (PEPCK), and glucose-6-phosphatase (G-6-Pase) as well as the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and C reactive protein (CRP) decreased.
  
  
  CONCLUSIONS
  The mechanism by which treatment with AME improves insulin resistance in HepG2 cells may involve the PI3K-Akt signaling pathway, the processes of glucose oxygenolysis, glycogen synthesis, gluconeogenesis and inflammatory cytokine expression.
authors.affiliation: School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China. Zhengxk.2006@163.com.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China. keyingying1988@sina.com.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Center for Artery Atheroscerosis Research, Havana University of Medical Sciences, Havana 999075, Cuba. fengaozi1987@sina.com.
authors.forename: Aozi
authors.initials: A
authors.lastname: Feng
authors.affiliation: School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China. 15136153630@163.com.
authors.forename: Peipei
authors.initials: P
authors.lastname: Yuan
authors.affiliation: School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China. zhoujj1988326@sina.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China. ku_rong@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China. wxl_325@163.com.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China. fwsh@hactcm.edu.cn.|Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China. fwsh@hactcm.edu.cn.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Feng
mesh_terms: D044946:Biflavonoids / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000008:administration & dosage; D007333:Insulin Resistance / Q000235:genetics*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D044946:Biflavonoids; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D007328:Insulin; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; C011164:amentoflavone; D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D005947:Glucose
keywords: AME; PI3K-Akt; glucose metabolism; inflammatory cytokines; insulin resistance