Ginsenoside Rg2 Attenuates Doxorubicin-induced Cardiomyocyte Apoptosis via the PI3K/Akt Pathway

Abstract

AbstractDoxorubicin, sold under the brand name Adriamycin among others, is an important drug for cancer therapy; however, its use is limited by its cardiotoxicity. Ginsenoside Rg2 is extracted from Panax ginseng C.A.Mey., Araliaceae, which is believed to have cardioprotective properties. However, to date, there have been no reports on whether ginsenoside Rg2 could protect cardiomyocytes against doxorubicin. In this study, we investigated the action and the underlying mechanisms of cardioprotection of ginsenoside Rg2 upon doxorubicin treatment. Cell counting kit-8 was used to determine cell viability; in addition, terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling staining was used to detect apoptotic cells. Western blotting was used to investigate the relevant pathways. LY294002, a phosphatidylinositol 3-kinase inhibitor, was also used in this study. Ginsenoside Rg2 significantly (p < 0.01) neutralized cardiomyocyte apoptosis induced by doxorubicin in a dose-dependent manner, but this effect was blocked by LY294002. Furthermore, ginsenoside Rg2 upregulated protein kinase B phosphorylation through the phosphatidylinositol 3-kinase/protein kinase B pathway and inhibited p53 expression. These results suggest that ginsenoside Rg2 could attenuate doxorubicin-induced cardiomyocyte apoptosis via the phosphatidylinositol 3-kinase/protein kinase B pathway. Graphical abstract