Gypenoside XVII protects against Myocardial Ischemia and Reperfusion Injury by inhibiting ER Stress-induced Mitochondrial Injury

Abstract Background Effective strategies are dramatically needed to prevent and improve the recovery from myocardial ischemia and reperfusion (I/R) injury. Direct interactions between the mitochondria and endoplasmic reticulum (ER) during heart diseases have been recently investigated. This study was designed to explore the cardioprotective effects of gypenoside XVII (GP-17) against I/R injury. The roles of ER stress, mitochondrial injury and their crosstalk within I/R injury and inGP-17-induced cardioprotection are also explored. Methods Cardiac contractility function was recorded in Langendorff-perfused rat hearts. The effects of GP-17 on mitochondrial function including mPTP opening, reactive oxygen species (ROS) production, and respiratory function were determinedusing fluorescence detection kits on mitochondria isolated from the rat hearts.H9c2 cardiomyocytes were used to explore the effects of GP-17 on hypoxia/reoxygenation. Results We found that GP-17inhibits myocardial apoptosis, reduces cardiac dysfunction, and improves contractile recovery in rat hearts. Our results also demonstrate that apoptosis induced by I/R is predominantly mediated by ER stress and associated with mitochondrial injury. Moreover, the cardioprotective effects of GP-17 are controlled by the PI3K/AKT and P38 signaling pathways. Conclusion GP-17 inhibits I/R-induced mitochondrial injuryby delaying the onset of ER stress through the PI3K/AKT and P38 signaling pathways.