Leonurus japonicus Houtt Attenuates Nonalcoholic Fatty Liver Disease in Free Fatty Acid-Induced HepG2 Cells and Mice Fed a High-Fat Diet

Nutrients. 2017 Dec 25;10(1):20. doi: 10.3390/nu10010020.

Abstract

We investigated the effects of a Leonurus japonicus ethanol extract (LJE) on nonalcoholic fatty liver disease (NAFLD). An in vitro model of hepatic steatosis was treated with 1 mM free fatty acid (FFA) in HepG2 cells. An in vivo NAFLD model was established using C57BL/6 mice fed a high-fat diet (HFD) and administered LJE (100 or 200 mg/kg) orally for 14 weeks. LJE treatment suppressed lipid accumulation and intracellular triglyceride levels significantly in a concentration-dependent manner in HepG2 cells. Moreover, LJE significantly reduced the expression of sterol regulatory element binding protein 1-c, and its downstream genes, which are associated with lipogenesis, in HepG2 cells. In HFD-fed mice, LJE treatment decreased body weight significantly and decreased serum alanine transaminase levels to normal values, concurrent with a decrease in hepatic lipid accumulation. Furthermore, LJE supplementation ameliorated insulin sensitivity by decreasing serum glucose and insulin levels. LJE improved hepatic steatosis by increasing the expression of phosphorylated AMP-activated protein kinase and peroxisome proliferator-activated receptor-α in HFD-fed mice and FFA-treated HepG2 cells. The results suggested that LJE might be a potential therapeutic agent to treat NAFLD.

Keywords: HepG2 cells; Leonurus japonicus; free fatty acids; high-fat diet; nonalcoholic fatty liver disease; obesity.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cell Survival / drug effects
  • Cytoprotection
  • Diet, High-Fat*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Fatty Acids, Nonesterified / toxicity*
  • Hep G2 Cells
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Insulin / blood
  • Insulin Resistance
  • Leonurus* / chemistry
  • Lipogenesis / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / prevention & control*
  • PPAR alpha / metabolism
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Time Factors
  • Triglycerides / metabolism
  • Weight Loss / drug effects

Substances

  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Insulin
  • PPAR alpha
  • Plant Extracts
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • AMP-Activated Protein Kinases