{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T07:45:24Z","timestamp":1791791124968,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,9,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Type 2 diabetes mellitus (T2DM) significantly amplifies the risk and severity of myocardial ischemia\u2013reperfusion (IR) injury, contributing to the disproportionately high cardiovascular mortality observed in diabetic patients. This study investigated the combined cardioprotective effects of sinomenine and liraglutide in a rat model of T2DM with myocardial IR injury and elucidated the underlying molecular mechanisms. Male Sprague Dawley rats were induced to T2DM with a high\u2010fat diet and low\u2010dose streptozotocin. After the induction of diabetes, the rats underwent 30\u2009min of occlusion of the left anterior descending coronary artery, followed by 24\u2009h of reperfusion. Before the IR procedure, diabetic rats were pretreated with sinomenine and\/or liraglutide for 7\u2009days. A comprehensive suite of techniques was employed to evaluate various endpoints, including echocardiographic and hemodynamic profiles, infarct size, histopathological alterations, cardiac troponin I (cTn\u2010I) levels, pyroptosis\u2010related proteins (NLRP3 and cleaved caspase\u20101), mitophagy\u2010related markers (PINK\u20101 and Parkin), oxidative stress indicators (MDA, SOD, and GPx), and pro\u2010inflammatory cytokines (IL\u201018 and IL\u20101\u03b2). The combination of sinomenine and liraglutide significantly improved cardiac function, reduced infarct size, attenuated histopathological damage, and decreased serum cTn\u2010I levels (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). It also downregulated the expression of pyroptosis\u2010related proteins, upregulated the expression of mitophagy\u2010related proteins, mitigated oxidative stress, and reduced pro\u2010inflammatory cytokine levels (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). The cardioprotective effects of the combined therapy were largely abrogated by pretreatment with mitochondrial division inhibitor 1. The combination of sinomenine and liraglutide showed remarkable cardioprotective effects against IR injury in diabetic rats, which were associated with the the attenuation of NLRP3\u2010driven pyroptosis and the enhancement of PINK\u20101\/Parkin\u2010mediated mitophagy, suggesting a mechanistic link warranting further validation.\n                  <\/jats:p>","DOI":"10.1096\/fj.202602960r","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:30:19Z","timestamp":1789806619000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Dual Therapy for Diabetic Ischemic Heart Injury: Sinomenine and Liraglutide Restore Mitochondrial Homeostasis and Suppress Pyroptosis"],"prefix":"10.1096","volume":"40","author":[{"given":"Bingsong","family":"Duan","sequence":"first","affiliation":[{"name":"Cardiac Surgery First Affiliated Hospital of Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8706-3140","authenticated-orcid":false,"given":"Ruolin","family":"Han","sequence":"additional","affiliation":[{"name":"Endocrinology Department 1 First Affiliated Hospital of Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155649"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201600112"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2024.2333440"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102022"},{"key":"e_1_2_11_6_1","first-page":"57","article-title":"Diabetes Mellitus: Understanding the Pathophysiology and Therapeutic Strategies","volume":"1","author":"Gupta A.","year":"2024","journal-title":"Journal of Clinical Advances and Research Reviews"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-021-00893-5"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.967115"},{"key":"e_1_2_11_9_1","first-page":"2001","volume-title":"Translating Cardioprotection for Patient Benefit: The EU\u2010CARDIOPROTECTION COST Action","author":"Hausenloy D. 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