{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:54:16Z","timestamp":1792173256522,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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>Myocardial ischemia\u2013reperfusion (I\/R) injury remains a major limitation in cardiovascular therapy, where restoration of blood flow paradoxically initiates oxidative stress, inflammation, mitochondrial dysfunction, and cardiomyocyte death. Although multiple pharmacological strategies have been investigated, clinical translation remains limited by inconsistent efficacy and incomplete pathway coverage. Quercetin, a naturally occurring flavonoid with pleiotropic biological activity, has attracted increasing interest as a potential modulator of I\/R\u2010associated injury. This systematic review evaluated current evidence regarding the cardioprotective effects and mechanistic actions of quercetin in myocardial I\/R injury. A structured literature search identified 25 eligible studies comprising predominantly preclinical in vivo animal investigations, together with limited ex vivo, in vitro, and clinical evidence. Across studies, quercetin consistently reduced infarct size, attenuated myocardial injury biomarkers, and improved cardiac functional parameters. Mechanistically, these effects were associated with suppression of oxidative stress and inflammatory signaling, particularly through modulation of ROS generation, NF\u2010\u03baB activation, PI3K\/Akt signaling, mitochondrial dysfunction, and apoptosis\u2010related pathways. Several studies also demonstrated preservation of endogenous antioxidant systems and mitochondrial integrity. However, substantial heterogeneity in experimental design, limited mitochondrial\u2010specific analyses, and the scarcity of comparative clinical studies remain major barriers to translation. Collectively, current evidence supports quercetin as a multi\u2010pathway cardioprotective candidate in myocardial I\/R injury, although further standardized and clinically oriented investigations are required to clarify its therapeutic relevance.<\/jats:p>","DOI":"10.1002\/jbt.71130","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:29:33Z","timestamp":1791296973000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quercetin in Myocardial Ischemia\u2013Reperfusion Injury: Mechanistic Evidence, Cardioprotective Effects, and Translational Challenges"],"prefix":"10.1002","volume":"40","author":[{"given":"Rony Abdi","family":"Syahputra","sequence":"first","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy, Universitas Sumatera Utara Medan Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5377-2052","authenticated-orcid":false,"given":"Princella","family":"Halim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy, Universitas Sumatera Utara Medan Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasniwiati Sari","family":"Hasibuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy, Universitas Sumatera Utara Medan Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adhayani","family":"Lubis","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Univeritas Prima Indonesia Medan Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00068-007-7152-z"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-4431.2004.04004.x"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.11455"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v3.i6.186"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.89942"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01827-6"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.01.025"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c160006"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.01.014"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62874"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2507"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20205034"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01688-x"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.03.008"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.924629"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1021624520740"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01757-9"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00956"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2010.186"},{"issue":"5","key":"e_1_2_13_21_1","first-page":"1273","article-title":"Quercetin Attenuates Myocardial Ischemia\u2010Reperfusion Injury via Downregulation of the HMGB1\u2010TLR4\u2010NF\u2010\u03baB Signaling Pathway","volume":"10","author":"Dong L. 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