Salidroside attenuates myocardial ischemia/reperfusion injury via AMPK-induced suppression of endoplasmic reticulum stress and mitochondrial fission.

Ischemic heart disease (IHD) is the primary cause of death worldwide. Salidroside (Sal), the major active compound derived from Rhodiola rosea, is believed to have cardioprotective effects. AMP-activated protein kinase (AMPK), is a pivotal AMP-activated protein kinase in energy metabolism. Whether Sal plays an anti-endoplasmic reticulum stress/mitochondrial fission role through AMPK remains elusive. In this study, we established a myocardial ischemia/reperfusion (I/R) rat model. Rat hearts exposed to Sal with or without compound C were then subjected to I/R. Further, H9c2 cardiomyocytes were subjected to simulated ischemia/reperfusion (SIR) by hypoxia-reoxygenation. The rats and cardiomyocytes were pretreated with Sal, followed by Compound C and AMPK-siRNA to block AMPK activity. We found that Sal significantly ameliorated cardiac function, mitigated infarct size and serum content of lactate dehydrogenase and creatine kinase, improved mitochondrial function, and reduced mitochondrial fission and apoptosis. Furthermore, in cultured H9c2 cardiomyocytes, Sal increased the cell viability and inhibited SIR-induced myocardial apoptosis and mitochondrial fission. Furthermore, the translocation of Drp1 from the cytoplasm to mitochondria induced by salidroside was confirmed both in vivo and in vitro. However, the use of Compound C or AMPK siRNA to block AMPK activity leads to blockade of the protective effects of Sal. In summary, protects against myocardial I/R by activating the AMPK signaling pathway, inhibiting ER stress, and reducing mitochondrial fission and apoptosis.