Antrodan Alleviates High-Fat and High-Fructose Diet-Induced Fatty Liver Disease in C57BL/6 Mice Model via AMPK/Sirt1/SREBP-1c/PPARγ Pathway

Int J Mol Sci. 2020 Jan 6;21(1):360. doi: 10.3390/ijms21010360.

Abstract

Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified β-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects. Considering the already well-known alleviating bioactivity of A. cinnamomea for the alcoholic steatohepatitis (ASH), we propose that Ant can be beneficial to NAFLD, and that the AMPK/Sirt1/PPARγ/SREBP-1c pathways may be involved in such alleviations. To uncover this, we carried out this study with 60 male C57BL/6 mice fed high-fat high-fructose diet (HFD) for 60 days, in order to induce NAFLD/NASH. Mice were then grouped and treated (by oral administration) as: G1: control; G2: HFD (HFD control); G3: Ant, 40 mgkg (Ant control); G4: HFD+Orlistat (10 mg/kg) (as Orlistat control); G5: HFD+Ant L (20 mg/kg); and G6: HFD+Ant H (40 mg/kg) for 45 days. The results indicated Ant at 40 mg/kg effectively suppressed the plasma levels of malondialdehyde, total cholesterol, triglycerides, GOT, GPT, uric acid, glucose, and insulin; upregulated leptin, adiponectin, pAMPK, Sirt1, and down-regulated PPARγ and SREBP-1c. Conclusively, Ant effectively alleviates NAFLD via AMPK/Sirt1/CREBP-1c/PPARγ pathway.

Keywords: Antrodan; Antrodia cinnamomea; hepatoprotective; high-fat-high-fructose diet; non-alcoholic fatty liver disease (NAFLD), insulin; orlistat.

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Administration, Oral
  • Animals
  • Antrodia / chemistry
  • Diet, High-Fat / adverse effects
  • Fructose / adverse effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / metabolism
  • PPAR gamma / metabolism*
  • Plant Extracts / administration & dosage
  • Plant Extracts / therapeutic use*
  • Protein Kinases / metabolism*
  • Signal Transduction
  • Sirtuin 1 / metabolism*
  • Sterol Regulatory Element Binding Protein 1 / metabolism*

Substances

  • PPAR gamma
  • Plant Extracts
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Fructose
  • Protein Kinases
  • AMP-Activated Protein Kinase Kinases
  • Sirt1 protein, mouse
  • Sirtuin 1