Hyperoside prevents sepsis-associated cardiac dysfunction through regulating cardiomyocyte viability and inflammation via inhibiting miR-21

Abstract

BackgroundSepsis-associated cardiac dysfunction results in increased mortality. Hyperoside (Hyp) is a flavonoid, showing significant anti-inflammatory effects. However, its pharmacological effects on sepsis-induced cardiac dysfunction remain unknown. In this study, we attempted to explore whether Hyp could prevent cardiac dysfunction and its underlying mechanisms. MethodsWe established a mice mode of sepsis by cecal ligation and puncture (CLP) treatment, and constructed a cell model of myocardial injury by lipopolysaccharide (LPS) stimulation. The cardiac function indicators and the inflammatory cytokine levels were measured. Effect of Hyp on cardiomyocyte viability was evaluated using MTT assay. The expression and functional role of microRNA-21 (miR-21), a documented molecule that regulated by Hyp, was evaluated in the constructed models, and the potential targets of miR-21 were predicted. ResultsHyp alleviated the impaired cardiac function and stimulated inflammation caused by CLP in the in vivo sepsis model, and alleviated the LPS-induced decrease in cell viability and increase in inflammation of cardiomyocytes. Additionally, Hyp significantly inhibited the expression of miR-21 in LPS-induced cardiomyocytes, and the increased cell viability and decreased inflammation caused by Hyp in the in vitro model could be reversed by miR-21 overexpression. In animal model of sepsis, the protective influence of Hyp against sepsis-induced cardiac dysfunction was attenuated by miR-21 upregulation. ConclusionOur findings demonstrated that Hyp may serve as a promising natural drug for the treatment of sepsis-associated cardiac dysfunction, and its protective role may exerted through regulating cardiomyocyte viability and inflammation by suppressing miR-21.