North American ginseng protects the heart from ischemia and reperfusion injury via upregulation of endothelial nitric oxide synthase.

Emerging evidence suggests ginseng has therapeutic potential in cardiovascular disease. The aim of this study was to investigate the role of endothelial nitric oxide synthase (eNOS) in the cardioprotective effects of ginseng during myocardial ischemia and reperfusion (I/R). Treatment with ginseng extract significantly increased Akt phosphorylation and eNOS protein levels in cultured neonatal cardiomyocytes. Upregulation of eNOS was blocked by LY294002, a PI3-kinase inhibitor, suggesting a PI3-kinase/Akt-dependent mechanism. To simulate I/R, cultured neonatal cardiomyocytes from eNOS(-/-) and wild-type (WT) mice were subjected to anoxia and reoxygenation (A/R). Ginseng treatment inhibited A/R-induced apoptosis in WT, but not in either eNOS(-/-) cardiomyocytes or WT cardiomyocytes treated with LY294002. To further study the cardioprotective effects of ginseng in vivo, WT and eNOS(-/-) mice were pretreated with ginseng extract (50mg/kg/day, oral gavage) for 7 days before they were subjected to myocardial I/R. Treatment with ginseng significantly increased Akt phosphorylation and eNOS protein levels in the myocardium. Furthermore, ginseng-induced myocardial eNOS expression was inhibited by LY294002. Strikingly, ginseng treatment significantly decreased infarct size and myocardial apoptosis following I/R in WT mice, but not in either eNOS(-/-) mice or WT mice treated with LY294002. We conclude that ginseng treatment protects the heart from I/R injury via upregulation of eNOS expression. Our study suggests that ginseng may serve as a potential therapeutic agent to limit myocardial I/R injury.