{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:53:42Z","timestamp":1792173222983,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Eupatilin confers cardioprotection against myocardial ischemia\u2010reperfusion injury (MIRI). Cyclooxygenases (COXs) serve as key rate\u2010limiting enzymes for prostaglandin biosynthesis. This study investigated the effects of eupatilin on COXs.<\/jats:p>\n                  <jats:p>H9c2 cells subjected to oxygen\u2010glucose deprivation\/reoxygenation (OGD\/R) were treated with graded doses of eupatilin, with aspirin serving as the positive control. Cellular reactive oxygen species (ROS), cell viability, and COX1\/COX2 protein expression were subsequently detected. In\u2010vivo acute MIRI was established in rats by 30\u2010min ligation of the left anterior descending coronary artery followed by reperfusion. MIRI\u2010modeled rats received eupatilin or aspirin treatment. Cardiac function was evaluated by echocardiography. Levels of prostaglandin E2 (PGE2), thromboxane A2 (TXA2), and cardiac troponin I (cTnI) were quantified by ELISA. Myocardial infarct size was assessed by TTC staining, and collagen deposition was determined by Masson staining. Immunohistochemistry was performed to detect myocardial COX1 and COX2 expression.<\/jats:p>\n                  <jats:p>In OGD\/R\u2010injured H9c2 cells, eupatilin dose\u2010dependently restored cell viability and suppressed cellular ROS overproduction. It suppressed OGD\/R\u2010induced upregulation of COX1 and COX2 and increased phosphorylation of Akt1 (S473) and GSK\u20103\u03b2 (S9). Molecular docking revealed favorable binding affinity between eupatilin and COXs. In MIRI\u2010model rats, deteriorated cardiac function was accompanied by increased PGE2, TXA2 and cTnI, as well as aggravated myocardial infarction and collagen deposition. Eupatilin administration alleviated myocardial injury by counteracting these pathological alterations. Moreover, eupatilin suppressed MIRI\u2010driven COX1\/COX2 overexpression and enhanced Akt1\u2010GSK\u20103\u03b2 phosphorylation.<\/jats:p>\n                  <jats:p>Eupatilin alleviate acute MIRI via COXs inhibition and activation of the Akt\/GSK\u20103\u03b2 pathway, providing a theoretical basis for its application against MIRI.<\/jats:p>","DOI":"10.1002\/jbt.71111","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:47:16Z","timestamp":1790070436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Eupatilin Alleviates Acute Myocardial Ischemia\u2010Reperfusion Injury in Rats via the Akt\/GSK\u20103\u03b2 Pathway by Targeting COXs"],"prefix":"10.1002","volume":"40","author":[{"given":"Min","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Shandong Healthcare Group Zibo Hospital Zibo 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