Costunolide alleviates hyperglycaemia‐induced diabetic cardiomyopathy via inhibiting inflammatory responses and oxidative stress

Hyperglycaemia‐induced myocardial injury promotes the induction of heart failure in diabetic patients. Impaired antioxidant capability and sustained chronic inflammation play a vital role in the progression of diabetic cardiomyopathy (DCM). Costunolide (Cos), a natural compound with anti‐inflammatory and antioxidant properties, has exhibited therapeutic effects in various inflammatory diseases. However, the role of Cos in diabetes‐induced myocardial injury remains poorly understood. In this study, we investigated the effect of Cos on DCM and explored the potential mechanisms. C57BL/6 mice were administered intraperitoneal streptozotocin for DCM induction. Cos‐mediated anti‐inflammatory and antioxidation activities were examined in heart tissues of diabetic mice and high glucose (HG)‐stimulated cardiomyocytes. Cos markedly inhibited HG‐induced fibrotic responses in diabetic mice and H9c2 cells, respectively. The cardioprotective effects of Cos could be correlated to the reduced expression of inflammatory cytokines and decreased oxidative stress. Further investigations demonstrated Cos reversed diabetes‐induced nuclear factor‐κB (NF‐κB) activation and alleviated impaired antioxidant defence system, principally via activation of nuclear factor‐erythroid 2 p45‐related factor‐2 (Nrf‐2). Cos alleviated cardiac damage and improved cardiac function in diabetic mice by inhibiting NF‐κB‐mediated inflammatory responses and activating the Nrf‐2‐mediated antioxidant effects. Therefore, Cos could be a potential candidate for the treatment of DCM.