Tectorigenin relieved sepsis-induced myocardial ferroptosis by inhibiting the expression of Smad3.

Abstract

Myocardial injury is a serious consequence of sepsis that contributes to high rates of death. Currently, the pathophysiology of cardiac damage in sepsis is still unknown, and treatment approaches are limited. The sepsis mouse model was established inducing by Lipopolysaccharide (LPS) in vivo and Tectorigenin was pretreated to explore whether it contributed to alleviated myocardial injury. Hematoxylin-eosin (HE) stain was employed to evaluate the myocardial injury severity. TUNEL assay measured the number of apoptosis cells and the levels of B-cell lymphoma-2 associated X (Bax) and Cleaved Caspase-3 were assessed by western blot. The contents of iron and related ferroptosis molecules (acyl-CoA synthetase long-chain family (ACSL4), Glutathione Peroxidase 4 (GPX4)) were assessed. Then, interleukin-1β (IL-1β), IL-18, IL-6, tumor necrosis factor-α (TNF-α), and other inflammatory-related cytokines were detected by ELISA. The expression of the mother against decapentaplegic homolog 3 (Smad3) in heart tissues was evaluated by western blot and immunofluorescence. Tectorigenin alleviated myocardial dysfunction and myofibrillar disruption in LPS-related sepsis groups. Tectorigenin ameliorated cardiomyocyte apoptosis and myocardial ferroptosis in LPS-stimulated sepsis mice. Tectorigenin reduced inflammatory-relevant cytokines in the cardiac tissues of LPS stimuli mice. In addition, we further confirm that Tectorigenin relieved myocardial ferroptosis by inhibiting the expression of Smad3. Tectorigenin ameliorates myocardial damage stimulated by LPS and this effect exerts by inhibiting ferroptosis and the inflammation of the myocardium. Furthermore, the inhibitory effect of Tectorigenin on ferroptosis may deregulate Smad3 expression. Taken together, Tectorigenin may be a viable method for alleviating myocardial damage in sepsis.