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This study investigates the mechanism by which the flavonoid compound Cirsiliol improves DCM by regulating the peroxisome proliferator-Activated receptor \u03b1 (PPAR-\u03b1)\/AMP-activated protein kinase (AMPK) signaling pathway. Using a high-glucose-treated H9C2 myocardial cell model and a streptozotocin-induced diabetic mouse model, the results show that Cirsiliol can dose-dependently increase myocardial cell survival, inhibit high-glucose-induced apoptosis, and significantly improve cardiac function in diabetic mice. Mechanistic studies indicate that Cirsiliol activates the PPAR-\u03b1\/AMPK pathway, upregulates the expression of key fatty acid oxidation enzymes carnitine palmitoyltransferase 1 (CPT1) and p-acetyl-CoA carboxylase (ACC), restores mitochondrial membrane potential, reduces lipid peroxidation product malondialdehyde (MDA) levels, enhances superoxide dismutase activity, and inhibits the release of inflammatory factors such as Interleukin 6 (IL-6) and Tumor Necrosis Factor \u03b1 (TNF-\u03b1). This study elucidates that Cirsiliol intervenes in energy metabolism imbalance, oxidative stress, and inflammatory responses through multiple targets, providing a new strategy for the treatment of DCM.<\/jats:p>","DOI":"10.1038\/s41598-025-32157-w","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T13:06:36Z","timestamp":1765458396000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cirsiliol alleviates diabetic cardiomyopathy by inhibiting oxidative stress and improving energy metabolism through the PPAR-\u03b1\/AMPK pathway"],"prefix":"10.1038","volume":"16","author":[{"given":"Jing","family":"Tao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunzhi","family":"Ling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanlin","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ru","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangling","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"32157_CR1","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.rceng.2019.10.012","volume":"222","author":"A Lorenzo-Almor\u00f3s","year":"2022","unstructured":"Lorenzo-Almor\u00f3s, A., Cepeda-Rodrigo, J. M. & Lorenzo, \u00d3. Diabetic cardiomyopathy. Rev. Clin. Esp. (Barc). 222, 100\u2013111. https:\/\/doi.org\/10.1016\/j.rceng.2019.10.012 (2022).","journal-title":"Rev. Clin. Esp. (Barc)"},{"key":"32157_CR2","doi-asserted-by":"publisher","first-page":"54","DOI":"10.12997\/jla.2025.14.1.54","volume":"14","author":"JE Lee","year":"2025","unstructured":"Lee, J. E., Kim, B. G. & Won, J. C. Molecular pathways in diabetic cardiomyopathy and the role of Anti-Hyperglycemic drugs beyond their glucose Lowering effect. J. Lipid Atheroscler.. 14, 54\u201376. https:\/\/doi.org\/10.12997\/jla.2025.14.1.54 (2025).","journal-title":"J. Lipid Atheroscler"},{"key":"32157_CR3","doi-asserted-by":"publisher","first-page":"436","DOI":"10.31083\/j.rcm2512436","volume":"25","author":"NH Siam","year":"2024","unstructured":"Siam, N. H., Snigdha, N. N., Tabasumma, N. & Parvin, I. Diabetes mellitus and cardiovascular disease: exploring Epidemiology, Pathophysiology, and treatment strategies. Rev. Cardiovasc. 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