Eupatilin modulates the Mcl-1 ubiquitination status and PI3K/Akt/Foxo3a pathway to inhibit apoptosis and alleviate sepsis-induced acute myocardial injury.

Sepsis-induced acute myocardial injury is a major cause of morbidity and mortality, characterized by inflammation, apoptosis, and impaired cardiomyocyte survival. Lipopolysaccharide (LPS)-induced cardiac injury models are commonly used to mimic sepsis and study its pathophysiological mechanisms. In this study, we investigated the protective effects of Eupatilin, a flavonoid compound derived from Artemisia argyi, on LPS-induced cardiac injury in rats and H9c2 cardiomyocyte cells. Our results show that Eupatilin significantly attenuated LPS-induced injury, as evidenced by increased cell viability, reduced inflammatory cytokine release, and decreased apoptosis. Mechanistically, we found that Eupatilin reduced the ubiquitination of Mcl-1, thereby promoting its stability and inhibiting apoptosis. Additionally, Eupatilin activated the PI3K/Akt signaling pathway, which led to the phosphorylation of Foxo3a, resulting in the retention of Foxo3a in the cytoplasm and the inhibition of apoptosis. These findings suggest that Eupatilin exerts protective effects against sepsis-induced myocardial injury by modulating Mcl-1 ubiquitination and activating the PI3K/Akt/Foxo3a pathway. Our study provides novel insights into the potential therapeutic application of Eupatilin in the treatment of sepsis-induced acute myocardial injury.