Resveratrol Ameliorates Cardiac Dysfunction by Inhibiting Apoptosis via the PI3K/Akt/FoxO3a Pathway in a Rat Model of Diabetic Cardiomyopathy

J Cardiovasc Pharmacol. 2017 Sep;70(3):184-193. doi: 10.1097/FJC.0000000000000504.


The aim of this study was to explore the effect and mechanism of action of resveratrol (RSV) on cardiac function in diabetic cardiomyopathy (DCM). Hyperglycemia-induced apoptosis contributes to the pathogenic changes in DCM. RSV treatment inhibited high glucose-induced apoptosis of neonatal rat ventricular myocytes. Additionally, high glucose decreased cell viability, prevented serine-threonine kinase (Akt) and FoxO3a phosphorylation, and suppressed cytoplasmic translocation of FoxO3a. However, these effects of apoptosis were reversed by 10 μM of RSV. The PI3K inhibitor LY294002 abolished the RSV protective effect in vitro. RSV (5 or 50 mg·kg·d orally for 8 weeks) prevented the deterioration of cardiac function and structural cardiomyopathy in a streptozotocin-induced rat model of diabetes and reduced apoptosis in diabetic myocardium. Furthermore, it restored streptozotocin-impaired phosphorylation of Akt and FoxO3a (p-Akt and p-FoxO3a) and suppressed nuclear translocation of FoxO3a in vivo. Together, these data indicate that RSV has therapeutic potential against DCM by inhibiting apoptosis via the PI3K/Akt/FoxO3a pathway.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Diabetic Cardiomyopathies / drug therapy*
  • Diabetic Cardiomyopathies / metabolism
  • Disease Models, Animal
  • Forkhead Box Protein O3 / antagonists & inhibitors*
  • Forkhead Box Protein O3 / metabolism
  • Male
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Stilbenes / pharmacology
  • Stilbenes / therapeutic use*


  • FOXO3 protein, rat
  • Forkhead Box Protein O3
  • Phosphoinositide-3 Kinase Inhibitors
  • Stilbenes
  • Proto-Oncogene Proteins c-akt
  • Resveratrol