Salidroside attenuates myocardial ischemia–reperfusion injury via PI3K/Akt signaling pathway

Abstract

To investigate the cardioprotective effects of salidroside on myocardial ischemia-reperfusion injury (IRI) in rabbits and the underlying action mechanisms in PI3K/Akt signaling pathway, a rabbit ischemia/reperfusion model was created by ligating the left anterior descending coronary arterial branch for 30 min and by releasing the ligature to allow reperfusion for 120 min. Salidroside or salidroside+PI3K inhibitor (LY294002) was administered via intracoronary injections at the onset of reperfusion. Apoptosis of cardiomyocytes was assessed by terminal dUTP nick-end labeling assay, and the expression of apoptosis-related proteins was observed by immunohistochemistry. The expressions of total Akt and phosphorylated Akt (p-Akt) were detected by western blot analysis. The results showed that intracoronary injection of salidroside at the onset of reperfusion markedly reduced the apoptosis of cardiomyocytes, significantly increasing Bcl-2 and p-Akt proteins expressions and decreasing Bax and caspase-3 expressions in the hearts subjected to ischemia followed by 120-min reperfusion. However, the anti-apoptotic effect induced by salidroside was inhibited by LY294002, which blocked the activation of Akt. These results suggested that intracoronary administration of salidroside at the onset of reperfusion could significantly reduce the IRI-induced apoptosis of cardiomyocytes, and this protective mechanism seemed to be mediated by the PI3K-Akt signaling pathway.

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

“…CHOP sensitizes cells to ER stress-induced apoptosis by causing an imbalance of Bcl-2 family members and then promoting cytochrome c release from the mitochondria to activate the apoptotic cascade ( 26 ). The results of the present study demonstrated that salidroside treatment reversed the H/R-induced upregulation of Bax expression and downregulation of Bcl-2 expression in H9c2 cells, which is consistent with the results of previous studies ( 29 , 38 ). These results indicate that salidroside may inhibit myocardial I/R injury by attenuating ER stress or ER stress-induced apoptosis by mitigating the mitochondria-dependent apoptotic pathway.…”

“…It has been demonstrated that ER stress contributes to cardiomyocyte apoptosis, which results in myocardial I/R and suppressing ER stress-associated apoptosis may be a critical therapeutic approach for treating myocardial I/R injury ( 19 , 28 , 29 ). Salidroside is an active ingredient extracted from Rhodiola rosea L ., which has various pharmacological functions, including anti-apoptosis, anti-oxidation and cardioprotection ( 30 ).…”

PGC-1: The Energetic Regulator in Cardiac Metabolism

“…Salidroside (SAL), an effective extracted component from R. crenulata, is a traditional Chinese medicine that has been recognized as a plant-derived adaptogen capable of maintaining physiological homeostasis upon exposure to stress. Accumulating evidence suggests that SAL has protective effects on many cardiac diseases such as myocardial I/R injury (Xu et al, 2013). Recently, Ping and colleagues have demonstrated that SAL improves myocardial mitochondrial respiratory function by stimulating the expression of PGC-1α-NRF-1/NRF-2 pathway during cardioprotection (Ping et al, 2015).…”

The Protective Effects of Salidroside from Exhaustive Exercise-Induced Heart Injury by Enhancing thePGC-1α–NRF1/NRF2Pathway and Mitochondrial Respiratory Function in Rats

“…Salidroside (SAL) is an effective extract component from R. crenulata . Many studies have found that SAL had protective effects on myocardial ischemia reperfusion [ 7 ], myocardial hypoxia [ 8 ], and myocardial injury [ 9 ]. Our previous research has suggested that SAL could improve hypoxia-induced cardiac myocyte energy metabolism by increasing the intracellular activity of the respiratory enzyme succinate dehydrogenase (SDH) [ 10 ].…”