{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T15:14:04Z","timestamp":1777734844395,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"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":["The Kaohsiung J of Med Scie"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Vaccarin is a naturally occurring flavonoid glycoside with cardioprotective properties; however, its involvement in myocardial ischemia\u2013reperfusion (MI\/R) injury remains poorly defined. We herein investigated whether vaccarin protects cardiomyocytes from MI\/R\u2010induced dysfunction in\u00a0vivo and in\u00a0vitro and examined the associated molecular mechanisms. To explore the protective effects of vaccarin, we established an MI\/R injury mouse model and in\u00a0vitro hypoxia\/reoxygenation (H\/R) injury model using H9c2 cardiomyocytes. In\u00a0vivo results showed that vaccarin alleviated MI\/R injury. In H9c2 cells, vaccarin partially reversed the H\/R\u2010induced elevation of reactive oxygen species and malondialdehyde levels and restored the reduced activity of superoxide dismutase. Vaccarin also suppressed the H\/R\u2010induced accumulation of Fe\n                    <jats:sup>2+<\/jats:sup>\n                    and glutathione disulfide while restoring the levels of glutathione, solute carrier family 7 member 11, and glutathione peroxidase 4. NADPH oxidase 4 (NOX4) was subsequently identified as a putative molecular target of vaccarin. Moreover, vaccarin inhibited H\/R\u2010induced activation of the Janus kinase 2 (JAK2)\/signal transducer and activator of transcription 3 (STAT3) signaling pathway in cardiomyocytes. NOX4 overexpression counteracted vaccarin\u2010mediated suppression of JAK2\/STAT3 signaling and blocked its antioxidative and antiferroptotic effects in H\/R\u2010treated cardiomyocytes. Collectively, these findings indicate that vaccarin confers cardioprotection against MI\/R injury by suppressing oxidative stress and ferroptosis, at least partly through inhibition of NOX4\u2010driven JAK2\/STAT3 signaling. These results suggest that vaccarin may be a promising therapeutic candidate for the treatment of MI\/R injury.\n                  <\/jats:p>","DOI":"10.1002\/kjm2.70226","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:12:08Z","timestamp":1777461128000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vaccarin Improves Myocardial Ischemia\u2013Reperfusion Injury by Attenuating Oxidative Stress and Ferroptosis Through Reducing\n                    <scp>NOX4<\/scp>\n                    \u2010Modulated\n                    <scp>JAK2<\/scp>\n                    \/\n                    <scp>STAT3<\/scp>\n                    Pathway Activation"],"prefix":"10.1002","author":[{"given":"Han","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Endocrinology Nanshi Hospital of Nanyang  Nanyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hand Microsurgery Changde First People's Hospital  Changde China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5563-9643","authenticated-orcid":false,"given":"Feng\u2010Cai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Public Health Chun'an First People's Hospital  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"issue":"1","key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s12872-023-03231-w","article-title":"The Global Prevalence of Myocardial Infarction: A Systematic Review and Meta\u2010Analysis","volume":"23","author":"Salari N.","year":"2023","journal-title":"BMC Cardiovascular 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ROS\/p38 MAPK Signaling","volume":"11","author":"Gong L.","year":"2019","journal-title":"American Journal of Translational Research"},{"issue":"3","key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.3892\/mmr.2016.4801","article-title":"Vaccarin Attenuates High Glucose\u2010Induced Human EA*hy926 Endothelial Cell Injury Through Inhibition of Notch Signaling","volume":"13","author":"Qiu Y.","year":"2016","journal-title":"Molecular Medicine Reports"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"114463","DOI":"10.1016\/j.intimp.2025.114463","article-title":"Vaccarin Alleviates Renal Ischemia\u2010Reperfusion Injury by Inhibiting Inflammation and Ferroptosis","volume":"153","author":"Fan Q.","year":"2025","journal-title":"International Immunopharmacology"},{"issue":"10","key":"e_1_2_7_15_1","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1161\/CIRCRESAHA.111.243972","article-title":"Biochemistry, Physiology, and Pathophysiology of 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