{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:06:28Z","timestamp":1791338788161,"version":"4.3.1"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>\n                      Prompt reperfusion is the standard treatment for acute myocardial infarction, but it can induce myocardial ischemia-reperfusion injury (MIRI). Quercetin, a plant-derived flavonoid, has been investigated as a potential cardioprotective agent in preclinical MIRI models; however, its effect magnitude, dose-exposure relevance, and mechanistic specificity remain uncertain. This systematic review and meta-analysis evaluated quercetin monotherapy in vivo and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      MIRI models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Databases were searched from inception to March 2026 for controlled preclinical studies comparing quercetin monotherapy with vehicle-treated MIRI controls. The primary endpoint was myocardial infarct size. Secondary outcomes included myocardial injury biomarkers, hemodynamic recovery, oxidative-stress markers, and inflammatory cytokines. Random-effects models calculated standardized mean differences (SMDs) or mean differences (MDs). Subgroup, leave-one-out, split-control, risk-of-bias-informed, dose-response meta-regression, and publication-bias analyses were performed where feasible. This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261325366).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty studies were included. Quercetin was associated with reduced infarct size compared with vehicle controls (SMD = \u22122.98, 95% confidence interval \u22124.37 to \u22121.58; P &amp;lt; 0.00001). A split-control sensitivity analysis showed an attenuated but directionally consistent effect (SMD = \u22122.22, 95% confidence interval \u22123.16 to \u22121.28). Exploratory dose-response meta-regression did not identify a clear linear association between systemic dose and infarct-size effect. Quercetin was associated with an 18.35-percentage-point improvement in left ventricular developed pressure (LVDP) recovery and favorable changes in selected maximal rates of pressure change (\u00b1dP\/dtmax). It was also associated with reduced myocardial injury biomarkers, decreased malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione (GSH), and lower tumor necrosis factor-alpha (TNF-\u03b1), interleukin-1 beta (IL-1\u03b2), and interleukin-6 (IL-6). Exploratory subgroup analyses suggested attenuated responsiveness in comorbid or metabolically altered models, but this finding was limited and confounded. Egger testing suggested possible small-study effects for infarct size.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Quercetin is associated with a directionally consistent preclinical cardioprotective signal in rodent\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      MIRI models. However, the magnitude, mechanistic specificity, and translational relevance remain uncertain because of heterogeneity, possible publication bias, unclear methodological quality, limited pharmacokinetic exposure data, and scarce sex-balanced, comorbid, and large-animal evidence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420261325366<\/jats:ext-link>\n                      , identifier CRD420261325366.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1863814","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:52:24Z","timestamp":1784699544000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Quercetin-associated cardioprotection in preclinical myocardial ischemia-reperfusion injury: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhao","family":"Shi","sequence":"first","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Liang","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Chen","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingye","family":"Wang","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongze","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Affiliated Hospital to Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Affiliated Hospital to Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Affiliated Hospital to Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1211\/jpp\/61.09.0014","article-title":"Enhancement of amlodipine cardioprotection by quercetin in ischaemia\/reperfusion injury in rats","volume":"61","author":"Ahmed","year":"2009","journal-title":"J. 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