Rhodiola wallichiana var.cholaensis protects against myocardial ischemia-reperfusion injury by attenuating oxidative stress-mediated apoptosis via enhancing Nrf2 signaling

The present study aimed to explore the cardioprotective effects of Rhodiola wallichiana var.cholaensis (RW) against hypoxia/reoxygenation (H/R)-induced H9c2 cell injury and ischemia/reperfusion (I/R)-induced myocardial injury. Following treatment with RW, H9c2 cells were subjected to 4 h of hypoxia/3 h of reoxyge-nation. MTT assay, LDH assay, and flow cytometry were employed to detect cell viability and changes of ROS and mitochondrial membrane potential. Moreover, after RW treatment, rats underwent 30 min of ischemia, followed by 120 min of reperfusion. Masson and TUNEL staining were performed to measure myocardial damage and apoptosis, respectively. The changes in the levels of proteins were detected by ELISA and western blot. The results showed that RW attenuated the H/R-induced increase in LDH release and loss of the mitochondrial membrane potential, as well as the apoptosis in H9c2 cells. Meanwhile, RW significantly reduces the ST-segment elevation and improves cardiomyocytes' injury, inhibit the apoptosis induced by I/R in rats. Furthermore, RW could decrease the levels of MDA and increase the levels of SOD, T-AOC. GSH-Px and GSH both in vivo and in vitro. Besides, RW increased the expressions of Nrf2, HO-1, ARE and NQO1, and decreased the expressions of Keap1, activating the Nrf2 signaling pathway. Taken together, these results suggested that RW exerts car-dioprotection on H/R injury in H9c2 cells and I/R injury in rats by attenuating oxidative stress-mediated apoptosis via enhancing Nrf2 signaling.