STAT3/FoxO3a/Sirt1 pathway inhibition by ginsenoside Rc ameliorates cardiomyocyte damage in septic cardiomyopathy by altering macrophage polarization

This study explored the role and mechanism of action of ginsenoside Rc in treating septic cardiomyopathy. Ginsenoside Rc mitigated LPS-induced oxidative stress, inflammation, Apoptosis, and mitochondrial dysfunction in cardiomyocytes and inhibited M1 polarization in macrophages. Ginsenoside Rc reduced the stimulating effect of M1-polarized macrophages on LPS-induced cardiomyocyte injury. Network pharmacological analysis suggested that ginsenoside Rc may play a role in septic cardiomyopathy through modulation of the STAT3/FoxO3a/SIRT1 pathway, which was validated in in vitro experiments. Ginsenoside Rc suppressed the expression of STAT3/FoxO3a pathway proteins and upregulated SIRT1. Moreover, influences of ginsenoside Rc on LPS-induced cardiomyocyte injury and macrophage polarization were abolished by ML115, a STAT3 agonist. In vivo, ginsenoside Rc notably improved myocardial injury and attenuated macrophage activation and inflammation in septic mice. Collectively, Ginsenoside Rc can ameliorate septic cardiomyopathy by modulating the STAT3/FoxO3a/SIRT1 pathway and altering macrophage polarization.

Ginsenoside Rc; Macrophage polarization; Mitochondrial dysfunction; STAT3; Septic cardiomyopathy.