Ginsenoside Rg1 protects cardiomyocytes from hypoxia-induced injury through the PI3K/AKT/mTOR pathway.

AIM

Myocardial ischemia (MI) is a leading cause of morbidity and mortality which makes the prevention and control of MI tremendously important. We aimed to explore the functional roles of ginsenoside (Gin) Rg1 in cardiomyocytes under hypoxia and to clarify underlying mechanisms.

MAIN METHODS

Hypoxia-induced H9c2 cell injury was evaluated by alterations of cell viability, apoptosis and autophagy. Then, effects of Gin Rg1 on hypoxia-induced cell injury were measured. The activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathways as well as expression of hypoxia-inducible factor 1α (HIF-1α) was determined with or without addition of PI3K or mTOR inhibitor. Finally, the effects of Gin Rg1 on rat ischemia/reperfusion (I/R) injury and underlying mechanism were studied.

KEY FINDINGS

First of all, hypoxia was identified to induce a decrease in cell viability and to increase cell apoptosis and autophagy. Then, these hypoxia-induced alterations were ameliorated by Gin Rg1, which had no effect on cell viability under normoxia. Subsequently, the phosphorylated levels of key kinases in the PI3K/AKT/mTOR pathways as well as expression of HIF-1α were all elevated by Gin Rg1. Activation of the PI3K/AKT/mTOR pathways and HIF-1α expression were inhibited by PI3K inhibitor, and activation of mTOR pathway and HIF-1α expression were inhibited by mTOR inhibitor. More in vivo experiments proved that Gin Rg1 ameliorated rat I/R injury through activating the PI3K/AKT/mTOR pathways.

SIGNIFICANCE

Gin Rg1 protected cardiomyocytes from hypoxia-induced cell injury by upregulating HIF-1α through activation of the PI3K/AKT/mTOR pathways.