Ginsenosides mixture from Panax ginseng C.A.Meyer improves CoCl2-induced oxidative stress and mitochondrial dysfunction through NAD+-dependent SIRT1 activation in cardiomyocytes

Abstract Introduction: There is growing recognition that medical therapies aimed at mediating mitochondrial ROS production may be important strategies to ameliorate cardiac disorders. Total ginsenosides (GS), a primary constituent extracted from Panax ginseng C.A.Meyer (ginseng) roots shows a strong therapeutic activity in heart disease and health benefits for hypoxia-related diseases. However, it is unclear whether GS protects hypoxic cardiomyocytes based on ROS production and mitochondrial function, as well as its molecular mechanism. Methods: In this study, mitochondrial respiratory function, ATP production, mitochondrial biosynthesis, glucose uptake, and NAD+-dependent SIRT1 activation in hypoxic and GS-pretreated H9c2 cells were investigated. Results: We found that GS protected cells from oxidative damage and also maintained normal mitochondrial function in CoCl2-stimulated cardiomyocytes. GS significantly reduced the glucometabolism disorder and mitochondrial respiration dysfunction as well. Further studies confirmed GS increased mitochondrial contents through regulating the NAD+ dependent SIRT1 activation, which was completely abrogated by nicotinamide. Importantly, we found that the ginsenoside Rg1, Re, Rf, Rb1, Rc and Rb2 are the key substances in GS associated with the anti-hypoxic action. Conclusion: This study may provide new insights into the protection of ginseng against cardiac hypoxia damage.