Xinshubao tablet ameliorates myocardial injury against heart failure via the DCN/PPARα/PGC-1α/P300 pathway

Abstract

Heart failure (HF) is a complex clinical syndrome with impaired ventricular ability due to structural or functional cardiac disorders. A traditional Chinese formula named Xinshubao tablet (XSB) is reported to protect cardiomyocytes and decrease the risk of HF clinically; however, the underlying mechanism of XSB on decreasing HF risk is not elucidated yet. Therefore, our study aimed to investigate the therapeutic efficacy and underlying mechanism of XSB by using HF model rats and H9c2 cells with oxygen glucose deprivation. Echocardiographic and pathological features of animal experiment showed that XSB treatment effectively improved cardiac function and ameliorated myocardial injury after 4 weeks of treatment. Cellular experiments indicated that XSB pretreatment significantly inhibited apoptosis and increased mitochondrial energy metabolism. Furthermore, in vivo and in vitro experiments both demonstrated that XSB suppressed oxidative stress and inflammatory response. Our results further revealed that the potential protective mechanism of XSB was closely associated with the DCN/PPARα/PGC-1α/P300 signaling pathway. Our findings provide novel mechanistic insights for HF treatment and a pharmacological basis for the therapeutic application of XSB against cardiovascular disorders.