Puerarin inhibits NHE1 activity by interfering with the p38 pathway and attenuates mitochondrial damage induced by myocardial calcium overload in heart failure rats

• Puerarin improves cardiac function and attenuates myocardial fibrosis and inflammation in adriamycin-induced heart failure rats. • Puerarin inhibits NHE1 activity and reduces intracellular Na+ and Ca2+ overload, thereby protecting mitochondria from calcium-induced damage. • Puerarin suppresses the p38 signaling pathway, leading to decreased expression of TGF-β and proinflammatory cytokines. • This study provides the first evidence that puerarin's cardioprotective mechanism involves inhibition of p38 and downstream NHE1, offering a potential therapeutic strategy for heart failure.