Salidroside mitigates hypoxia/reoxygenation injury by alleviating endoplasmic reticulum stress‑induced apoptosis in H9c2 cardiomyocytes.

Abstract

Endoplasmic reticulum (ER) stress-induced apoptosis serves a crucial role in the development of myocardial ischemia/reperfusion (I/R) injury. Salidroside is a phenylpropanoid glycoside isolated from Rhodiola rosea L., which is a plant often used in traditional Chinese medicine. It possesses multiple pharmacological actions and protects against myocardial I/R injury in vitro and in vivo. However, it is not yet clear whether ER stress or ER stress-induced apoptosis contributes to the cardioprotective effects of salidroside against myocardial I/R injury. Hence, hypoxia/reoxygenation (H/R)-treated H9c2 cardiomyocytes were used in the current study to mimic myocardium I/R injury in vivo. It was hypothesized that salidroside alleviates ER stress and ER stress-induced apoptosis, thereby reducing H/R injury in H9c2 cells. The results demonstrated that salidroside attenuated H/R-induced H9c2 cardiomyocyte injury, as cell viability was increased, lactate dehydrogenase release was decreased, morphological changes in apoptotic cells were ameliorated and the apoptosis ratio was reduced compared with the H/R group. ER stress was reversed, indicated by the downregulation of glucose regulated protein 78 and C/EBP homologous protein following pretreatment with salidroside. In addition, salidroside attenuated ER stress-induced apoptosis, as the expression of cleaved caspase-12 and pro-apoptotic protein Bcl-2 associated X protein and activity of caspase-3 was decreased, while the expression of anti-apoptotic protein Bcl-2 was increased following pretreatment with salidroside. Furthermore, the results indicated that salidroside decreases the activation of the ER stress-associated signaling pathway, as the expression of phosphorylated protein kinase RNA (PKR)-like ER kinase (p-PERK) and phosphorylated inositol-requiring enzyme-1α (p-IRE1α) proteins were decreased following pretreatment with salidroside. These results demonstrate that salidroside protects against H/R injury via regulation of the PERK and IRE1α pathways, resulting in alleviation of ER stress or ER stress-induced apoptosis in H9c2 cardiomyocytes.