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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\u2010inflammatory and antioxidant properties, has exhibited therapeutic effects in various inflammatory diseases. However, the role of Cos in diabetes\u2010induced 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\u2010mediated anti\u2010inflammatory and antioxidation activities were examined in heart tissues of diabetic mice and high glucose (HG)\u2010stimulated cardiomyocytes. Cos markedly inhibited HG\u2010induced 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\u2010induced nuclear factor\u2010\u03baB (NF\u2010\u03baB) activation and alleviated impaired antioxidant defence system, principally via activation of nuclear factor\u2010erythroid 2 p45\u2010related factor\u20102 (Nrf\u20102). Cos alleviated cardiac damage and improved cardiac function in diabetic mice by inhibiting NF\u2010\u03baB\u2010mediated inflammatory responses and activating the Nrf\u20102\u2010mediated antioxidant effects. Therefore, Cos could be a potential candidate for the treatment of DCM.<\/jats:p>","DOI":"10.1111\/jcmm.17686","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T04:40:22Z","timestamp":1677040822000},"page":"831-845","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Costunolide alleviates hyperglycaemia\u2010induced diabetic cardiomyopathy via inhibiting inflammatory responses and oxidative stress"],"prefix":"10.1111","volume":"27","author":[{"given":"Bo","family":"Jin","sequence":"first","affiliation":[{"name":"The Affiliated Xiangshan Hospital of Wenzhou Medical University  Ningbo China"},{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Chemical Biology Research Center, School of 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