Cardioprotective Natural Compound Pinocembrin Attenuates Acute Ischemic Myocardial Injury via Enhancing Glycolysis

• Published in: Oxidative medicine and cellular longevity 2020, Vol.2020 (2020), p.1-13
• Main Authors: Gu, Xuefeng, Yang, Bo, Wan, Guoqing, Zheng, Yanjun, Lin, Jingrong
• Format: Article
• Language: English
• Subjects: Animals; Cardiomyocytes; Cardiotonic Agents - pharmacology; Cardiovascular disease; Coronary vessels; Energy; Flavanones - pharmacology; Glucose; Glycolysis - drug effects; Heart attacks; Ischemia; Ischemic Preconditioning; Laboratory animals; Male; Metabolism; Mice; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - therapy; Myocardium - metabolism; Myocardium - pathology; Rats; Rats, Sprague-Dawley
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2020/4850328

Purpose. Emerging evidence has shown that pinocembrin protects the myocardium from ischemic injury in animals. However, it is unknown whether it has cardioprotection when given at the onset of reperfusion. Also, mechanisms mediating the cardioprotective actions of pinocembrin were largely unknown. Thus, this study is aimed at investigating the effects of pinocembrin postconditioning on ischemia-reperfusion (I/R) injury and the underlying mechanisms. Methods. The in vivo mouse model of myocardial I/R injury, ex vivo isolated rat heart with global I/R, and in vitro hypoxia/reoxygenation (H/R) injury model for primary cardiomyocytes were used. Results. We found that pinocembrin postconditioning significantly reduced the infarct size and improved cardiac contractile function after acute myocardial I/R. Mechanically, in primary cardiomyocytes, we found that pinocembrin may confer protection in part via direct stimulation of cardiac glycolysis via promoting the expression of the glycolytic enzyme, PFKFB3. Besides, PFKFB3 inhibition abolished pinocembrin-induced glycolysis and protection in cardiomyocytes. More importantly, PFKFB3 knockdown via cardiotropic adeno-associated virus (AAV) abrogated cardioprotective effects of pinocembrin. Moreover, we demonstrated that HIF1α is a key transcription factor driving pinocembrin-induced PFKFB3 expression in cardiomyocytes. Conclusions. In conclusion, these results established that the acute cardioprotective benefits of pinocembrin are mediated in part via enhancing PFKFB3-mediated glycolysis via HIF1α, which may provide a new therapeutic target to impede the progression of myocardial I/R injury.