{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T22:56:44Z","timestamp":1781218604139,"version":"3.54.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Hyperglycemia can lead to excessive production of reactive oxygen species (ROS), contributing to diabetes and its complications, such as diabetic cardiomyopathy (DCM). This study aims to elucidate the protective mechanisms of Curcumin (CUR) against hyperglycemia-induced cardiomyocyte injury. We constructed a high-glucose (HG) model using primary cardiomyocytes and determined the optimal concentration of CUR by assessing cell viability with the CCK-8 assay. Enzyme-linked assays were used to measure the activities of HO-1, T-SOD, and GSH-Px, investigating the antioxidant effects of the Nrf2 signaling pathway. Flow cytometry was employed to measure apoptosis and mitochondrial membrane potential (\u0394\u03a8m). Mitochondria were isolated from cardiomyocytes to examine cytosolic and mitochondrial cytochrome c (cytc) expression. Western blotting was used to analyze the expression levels of Nrf2, PI3K, AKT, Keap1, HO-1, Bcl-2, and Bax proteins. Our findings suggest that CUR enhanced the viability and antioxidant enzyme activity of primary cardiomyocytes under HG conditions, stabilized \u0394\u03a8m, reduced ROS production, and decreased apoptosis. Moreover, CUR alleviated HG-induced cardiomyocyte damage by upregulating Nrf2, PI3K, AKT, HO-1, and Bcl-2 expression, while downregulating Bax. These findings demonstrate that the protective effect of CUR against diabetic cardiac injury may be mediated through activation of the Nrf2 and PI3K\/AKT signaling pathways and upregulation of antioxidant enzyme expression, aiming to provide a theoretical foundation for further research into the therapeutic application of CUR in DCM.<\/jats:p>","DOI":"10.3389\/fphar.2026.1752397","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T22:10:25Z","timestamp":1781215825000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Curcumin protects high glucose-induced diabetic myocardial injury by regulating Nrf2 and PI3K\/AKT pathways"],"prefix":"10.3389","volume":"17","author":[{"given":"ZeYue","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University","place":["Nanjing, China"]},{"name":"School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhuangYin","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University","place":["Nanjing, China"]},{"name":"School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University","place":["Nanjing, China"]},{"name":"School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1696344","DOI":"10.3389\/fendo.2025.1696344","article-title":"Metabolic-stress-induced mitochondrial calcium dysregulation: a central hub in diabetic cardiomyopathy pathogenesis and treatment","volume":"16","author":"Deng","year":"2025","journal-title":"Front. 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