Salidroside Alleviates Myocardial Ischemia Reperfusion by Balancing Mitochondrial Homeostasis via Nrf2

Salidroside (SAL), a phenylpropanoid glycoside compound mainly from Rhodiola rosea, showed potential effects on myocardial ischemia reperfusion (MIRI) in our previous studies. The primary objective of this investigation was to study the mechanism by which SAL preserves mitochondrial homeostasis in order to provide protection against MIRI. The impact of SAL on the hypoxia/reoxygenation (H/R)-induced H9c2 cells was detected by using CCK-8, LDH, and AST. The number, function, and morphology of mitochondria were examined by TEM, RT-qPCR, and western blot. The binding ability between SAL and Nrf2 was explored through molecular docking and the cell thermal shift assay. Combined with the Nrf2 inhibitor ML385, our results demonstrated that SAL promotes mitochondrial protection by activating Nrf2, decreasing oxidative stress, and altering the AMPK/PGC-1 alpha/PPAR alpha pathway. In addition, SAL elevates ATP levels and improves mitochondrial dynamics imbalance by inducing both autophagy and mitophagy. These findings highlight the potential therapeutic benefits of SAL for cardiac health and the mitigation of MIRI.