2. Academic Validation
  3. Resveratrol protects against myocardial ischemic injury in obese mice via activating SIRT3/FOXO3a signaling pathway and restoring redox homeostasis

Resveratrol protects against myocardial ischemic injury in obese mice via activating SIRT3/FOXO3a signaling pathway and restoring redox homeostasis

  • Biomed Pharmacother. 2024 Mar 21:174:116476. doi: 10.1016/j.biopha.2024.116476.
Xi Zhu 1,  En Ma 1,  Yixuan Ge 1,  Meng Yuan 1,  Xiaowei Guo 1,  Jun Peng 1,  Weidong Zhu 2,  Dan-Ni Ren 3,  Da Wo 4
Affiliations

Affiliations

  • 1 Fujian Key Laboratory of Integrative Medicine on Geriatric, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.
  • 2 Fujian Key Laboratory of Integrative Medicine on Geriatric, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China; Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.
  • 3 Fujian Key Laboratory of Integrative Medicine on Geriatric, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China. Electronic address: danny1217@163.com.
  • 4 Fujian Key Laboratory of Integrative Medicine on Geriatric, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China; Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China. Electronic address: dwo_work@126.com.
PMID: 38520872 DOI: 10.1016/j.biopha.2024.116476
Abstract

Background: Increasing global overweight and obesity rates not only increase the prevalence of myocardial infarction (MI), but also exacerbate ischemic injury and result in worsened prognosis. Currently, there are no drugs that can reverse myocardial damage once MI has occurred, therefore discovering drugs that can potentially limit the extent of ischemic damage to the myocardium is critical. Resveratrol is a polyphenol known for its antioxidant properties, however whether prolonged daily intake of resveratrol during obesity can protect against MI-induced damage remains unexplored.

Methods: We established murine models of obesity via high-fat/high-fructose diet, along with daily administrations of resveratrol or vehicle, then performed surgical MI to examine the effects and mechanisms of resveratrol in protecting against myocardial ischemic injury.

Results: Daily administration of resveratrol in obese mice robustly protected against myocardial ischemic injury and improved post-MI cardiac function. Resveratrol strongly inhibited oxidative and DNA damage via activating SIRT3/FOXO3a-dependent antioxidant Enzymes following MI, which were completely prevented upon administration of 3-TYP, a selective SIRT3 Inhibitor. Hence, the cardioprotective effects of prolonged resveratrol intake in protecting obese mice against myocardial ischemic injury was due to reestablishment of intracellular redox homeostasis through activation of SIRT3/FOXO3a signaling pathway.

Conclusion: Our findings provide important new evidence that supports the daily intake of resveratrol, especially in those overweight or obese, which can robustly decrease the extent of ischemic damage following MI. Our study therefore provides new mechanistic insight and suggests the therapeutic potential of resveratrol as an invaluable drug in the treatment of ischemic heart diseases.

Keywords

Myocardial infarction; Obesity; Oxidative stress; Resveratrol; SIRT3/FOXO3a signaling.

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