Resveratrol Ameliorates Diabetes-Induced Cardiac Dysfunction Through AT1R-ERK/p38 MAPK Signaling Pathway

Cardiovasc Toxicol. 2016 Apr;16(2):130-7. doi: 10.1007/s12012-015-9321-3.


The present study was to determine the preventive effect of resveratrol (Res) on diabetes-induced cardiac dysfunction and the possible signaling pathway involved. Diabetes was induced in rats by injection of streptozotocin (STZ) at 45 mg/kg. The animals were randomly divided into three groups (10 rats/group): normal group, diabetes groups with or without Res (80 mg/kg) treatment. Biochemistry, cardiac function and fibrosis were detected. Moreover, pro-inflammatory cytokines were evaluated, and heart tissues were homogenized for western blot analysis to analyze the possible mechanisms. The results indicated that Res might regulate glucose and lipid metabolism, ameliorate cardiac function and fibrosis response in STZ-induced diabetic rats. The protective effects were consistent with the inhibition of inflammatory factors such as TNF-α, IL-6 and IL-1β. In addition, Res favorably shifted STZ-induced AT1R, ERK1/2 and p38 MAPK activation in rat heart. In conclusion, the results suggested that Res attenuated diabetes-induced cardiac dysfunction, and the effects were associated with attenuation inflammatory response and down-regulation of AT1R-ERK/p38 MAPK signaling pathway.

Keywords: AT1R-ERK/p38 MAPK; Diabetes-induced cardiac dysfunction; Glucose and lipid metabolism; Inflammation response; Resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Heart Diseases / drug therapy
  • Heart Diseases / metabolism*
  • Heart Diseases / pathology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1 / metabolism*
  • Resveratrol
  • Stilbenes / pharmacology
  • Stilbenes / therapeutic use*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Receptor, Angiotensin, Type 1
  • Stilbenes
  • p38 Mitogen-Activated Protein Kinases
  • Resveratrol