Artemisia capillaris formula inhibits hepatic steatosis via an miR‑122‑induced decrease in fatty acid synthase expression in vivo and in vitro

Mol Med Rep. 2016 Jun;13(6):4751-8. doi: 10.3892/mmr.2016.5131. Epub 2016 Apr 14.

Abstract

Non‑alcoholic fatty liver disease (NAFLD) is a widespread health concern, and there is currently insufficient understanding regarding its pathogenesis and treatment. The present study aimed to explore the effects of Artemisia capillaris formula (ACF) on high‑fat diet‑induced hepatic steatosis and fatty acid‑induced intracellular lipid accumulation, by micro (mi)RNA regulation. A total of 72 Sprague‑Dawley rats were divided into six groups (n=12/group). One group was designated as the control group and fed a normal diet, and the remaining five groups were allowed ad libitum access to a high‑fat diet for eight weeks, in order to establish an NAFLD rat model. The rats were subsequently administered polyene phosphatidylcholine (PP; 0.076 g/kg body weight/day), low dose of ACF (0.462 g/kg body weight/day), middle dose of ACF (0.924 g/kg body weight/day) or high dose of ACF (1.848 g/kg body weight/day) intragastrically for four weeks. HepG2 human hepatocellular carcinoma cells were treated with oleic acid and palm acid, followed by treatment with various concentrations of ACF. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC), high‑density lipoprotein cholesterol (HDL‑C), low‑density lipoprotein cholesterol (LDL‑C), and steatotic HepG2 human liver carcinoma cell TC and TG levels were measured. ACF and PP treatments attenuated high‑fat diet‑induced hepatic steatosis and fatty acid‑induced intracellular lipid accumulation. A modified high‑fat diet significantly increased ALT, AST, TG, TC, LDL‑C levels and decreased HDL‑C levels. Treatment with ACF and PP abrogated the increase in liver enzymes and TG, TC and LDL‑C levels, but did not influence HDL‑C levels in a high‑fat diet induced rat model of steotosis. Steatotic HepG2 cells exhibited significantly increased levels of both TG and TC. Treatment with ACF significantly decreased TC and TG levels in vivo, and ACF and PP treatment decreased the expression levels of fatty acid synthase (FASN) and increased miR‑122 in vivo and in vitro. In conclusion, these results suggested that ACF may inhibit hepatic steatosis via miR‑122‑induced downregulation of FASN in vivo and in vitro.

MeSH terms

  • Animals
  • Artemisia* / chemistry
  • Diet, High-Fat / adverse effects
  • Down-Regulation / drug effects*
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Fatty Acid Synthases / genetics*
  • Hep G2 Cells
  • Humans
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • MicroRNAs / genetics*
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / pathology
  • Rats, Sprague-Dawley

Substances

  • Drugs, Chinese Herbal
  • MIRN122 microRNA, rat
  • MicroRNAs
  • Fatty Acid Synthases