Anti-hyperlipidemic and anti-peroxidative role of pterostilbene via Nrf2 signaling in experimental diabetes

Eur J Pharmacol. 2016 Apr 15;777:9-16. doi: 10.1016/j.ejphar.2016.02.054. Epub 2016 Feb 24.

Abstract

Nuclear factor erythroid 2-related factor (Nrf2), a key transcription factor triggers the expression of antioxidant and detoxification genes thereby providing cellular protective functions against oxidative stress-mediated disorders. Recent research has identified that pharmacological activation of Nrf2 also regulates the largest cluster of genes associated with lipid metabolism. With this background, this paper highlights the anti-hyperlipidemic and anti-peroxidative role of pterostilbene (PTS), an Nrf2 activator, in streptozotocin (STZ)-induced diabetic model. PTS administration to diabetic mice for 5 weeks significantly regulated blood glucose levels through the elevation of insulin secretion. The circulatory and liver lipid profiles of total cholesterol (TC), triglycerides (TG) and non-esterified fatty acids (NEFA) were maintained to normal levels upon PTS treatment. Moreover, PTS administration also normalized the circulatory levels of very low-, low- and high density lipoprotein cholesterols (VLDL-, LDL-, HDL-C) and also reduced lipid peroxidation in STZ-induced diabetic mice. In addition, Nrf2 and its downstream targets, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) enzyme activities and glutathione (GSH) levels were significantly elevated in liver tissues of diabetic mice upon PTS administration. Further, H&E staining of diabetic mouse liver showed collapse in hepatic microvesicles due to altered lipid metabolism. Both structural and functional alterations were attenuated by PTS indicating its role in diabetic dyslipidemia through Nrf2-mediated mechanism that could be considered as a promising therapeutic agent.

Keywords: Diabetes; Dyslipidemia; Lipids; Nrf2; Pterostilbene; Streptozotocin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology*
  • Gene Expression Regulation / drug effects
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood
  • Lipid Peroxidation / drug effects*
  • Lipoproteins / blood
  • Lipoproteins / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Mice
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Signal Transduction / drug effects*
  • Stilbenes / pharmacology*
  • Stilbenes / therapeutic use

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Lipoproteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Stilbenes
  • pterostilbene