Majonoside-R2 Postconditioning Protects Cardiomyocytes Against Hypoxia/Reoxygenation Injury by Attenuating the Expression of HIF1α and Activating RISK Pathway.

Reoxygenation of hypoxic cardiac myocytes can paradoxically induce myocardial injury and affect the recovery processes. Pharmacological postconditioning is an efficient strategy used in clinical practice that protects cardiomyocytes from hypoxia/reoxygenation (HR) injury. Natural products or foods have been known to possess effective cardioprotective properties. Majonoside-R2 (MR2) is a dominant saponin component of Vietnamese ginseng that has several biological effects. In this study, we evaluated the protective effect of MR2 on HR-stimulated cardiomyocytes and investigated the related molecular mechanisms. H9C2 cardiomyocytes were exposed to HR conditions with or without MR2 supplementation. Samples from experimental groups were used to analyze the expression of apoptosis- and activating reperfusion injury salvage kinase (RISK)-related factors in response to HR injury by using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blotting. Post-treatment, MR2 enhanced cell viability under HR conditions. We found that MR2 suppressed the expression of hypoxia-inducible factor 1-alpha (HIF1α) and transforming growth factor beta 1 (TGFβ1), modulated Akt/GSK3ß/cAMP response element-binding signaling, and regulated gene expression related to apoptosis (B cell lymphoma-extra-large [Bcl-xl], Bcl-2 homologous killer [Bak], Bcl-2 associated X [Bax], and connexin 43 [Cnx43]). Thus, the present findings demonstrate that MR2 protects cardiomyocytes against HR injury by suppressing the expression of HIF1α and activating the RISK pathway.