Silymarin prevents lipid accumulation in the liver of rats with type 2 diabetes via sirtuin1 and SREBP-1c

J Basic Clin Physiol Pharmacol. 2018 Jun 27;29(3):301-308. doi: 10.1515/jbcpp-2017-0122.

Abstract

Background: In this study, we have investigated whether silymarin intake influences lipid and glycogen content in conjunction with sirtuin1 (SIRT1) and sterol regulatory element-binding protein 1c (SREBP-1c) expressions in liver of type 2 diabetic rat.

Methods: Thirty-six male Wistar rats were randomly divided into six groups: control groups (C) and diabetic groups (D); the control groups received 60 or 120 mg/kg silymarin (C+S60 or C+S120), and the diabetic groups received 60 or 120 mg/kg silymarin (D+S60 or D+S120) daily for 8 weeks. Serum biochemical parameters, as well as glycogen, lipid and oxidative stress biomarkers, in the liver tissue were measured by spectrophotometric methods. Additionally, SIRT1 and SREBP-1c messenger RNA (mRNA) expressions were evaluated by quantitative polymerase chain reaction.

Results: Diabetes caused a significantly increased fasting blood sugar, homeostasis model assessment for insulin resistance, liver total cholesterol and triglyceride (TG) content, which were attenuated after the administration of silymarin. Dietary silymarin caused the improvement of lipid content in the liver of diabetic rats. Moreover, silymarin administration promoted SIRT1, suppressed SREBP-1c mRNA expression, reduced liver nitric oxide and protein carbonyl content, and increased liver glycogen, catalase and glutathione peroxidase activity. Furthermore, histopathological changes were improved in the treated groups.

Conclusions: Silymarin administration considerably restored hepatic changes induced by streptozotocin and nicotinamide. The upregulation of SIRT1 mRNA expression by silymarin may be associated with decreased lipid, increased glycogen content and downregulation of the SREBP-1c gene in the liver.

Keywords: diabetes mellitus type 2; lipid; liver; silymarin; sterol regulatory element-binding protein-1c (SREBP-1c).

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dose-Response Relationship, Drug
  • Glycogen / metabolism
  • Lipid Metabolism / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Niacinamide / administration & dosage
  • Protective Agents / administration & dosage
  • Protective Agents / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Silymarin / administration & dosage
  • Silymarin / pharmacology*
  • Sirtuin 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Streptozocin / administration & dosage
  • Up-Regulation / drug effects

Substances

  • Protective Agents
  • RNA, Messenger
  • Silymarin
  • Srebf1 protein, rat
  • Sterol Regulatory Element Binding Protein 1
  • Niacinamide
  • Streptozocin
  • Glycogen
  • Sirt1 protein, rat
  • Sirtuin 1