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Several mechanisms have been proposed to contribute to the occurrence and persistence of DCM, in which oxidative stress and autophagy play a non\u2010negligible role. Diabetic cardiomyopathy is involved in a variety of physiological and pathological processes. The 5\u2032 adenosine monophosphate\u2010activated protein kinase\/nuclear factor\u2010erythroid 2\u2010related factor 2 (AMPK\/Nrf2) are expressed in the heart, and studies have shown that asiaticoside (ASI) and activated AMPK\/Nrf2 have a protective effect on the myocardium. However, the roles of ASI and AMPK\/Nrf2 in DCM are unknown. The intraperitoneal injection of streptozotocin (STZ) and high\u2010fat feed were used to establish the DCM models in 100 C57\/BL mice. Asiaticoside and inhibitors of AMPK\/Nrf2 were used for intervention. Cardiac function, oxidative stress, and autophagy were measured in mice. DCM mice displayed increased levels of oxidative stress while autophagy levels declined. In addition, AMPK\/Nrf2 was activated in DCM mice with ASI intervention. Further, we discovered that AMPK\/Nrf2 inhibition blocked the protective effect of ASI by compound C and treatment with ML\u2010385. The present study demonstrates that ASI exerts a protective effect against DCM via the potential activation of the AMPK\/Nrf2 pathway. Asiaticoside is a potential therapeutic target for DCM.<\/jats:p>","DOI":"10.1111\/jcmm.18055","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T19:16:26Z","timestamp":1703013386000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Cardioprotective effects of asiaticoside against diabetic cardiomyopathy: Activation of the AMPK\/Nrf2 pathway"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7033-3615","authenticated-orcid":false,"given":"Chennian","family":"Xu","sequence":"first","affiliation":[{"name":"Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy Air Force Medical University Xi'an Shaanxi China"},{"name":"Department of Cardiovascular Surgery, Xijing Hospital Air Force Medical University Xi'an Shaanxi 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