Abstract
BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) remains a pivotal clinical conundrum in clinical cardiovascular practice, accounting for a substantial proportion of morbidity and mortality associated with cardiovascular disorders. Puerarin, a natural isoflavone derived from kudzu root, has shown promising cardioprotective potential in preclinical studies. METHODS: Relevant studies were systematically searched in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, VIP Database, and Web of Science from inception to October 2025 for preclinical studies evaluating puerarin's effects on MIRI. Key outcome measures included myocardial infarction size, myocardial ischemic size, cardiac function parameters, myocardial injury markers, oxidative stress indicators, inflammatory cytokines, and the cardiomyocyte apoptosis index. Methodological quality was assessed using the SYRCLE risk-of-bias tool and GRADE tool, and meta-analyses were performed with RevMan 5.4.1 and STATA 18.0. RESULTS: A total of 29 eligible studies were included. This meta-analysis showed that puerarin administration reduced the myocardial infarction size and myocardial ischemic size, improved cardiac systolic/diastolic function (e.g., increased LVEF, LVSP, and LVFS; decreased LVIDd and LVEDP), attenuated myocardial injury (decreased cTn-T, CK, CK-MB, and LDH levels), suppressed oxidative stress (elevated SOD and NO; reduced MDA), inhibited inflammatory responses (decreased TNF-α, IL-1β, and IL-6; increased GSH), and reduced cardiomyocyte apoptosis. Subgroup analysis indicated potential influences of the administration route, dosage, and animal body weight on partial outcomes. CONCLUSION: Preclinical evidence demonstrates that puerarin exerts cardioprotective effects against MIRI through multi-target mechanisms, including mitigating oxidative stress, suppressing inflammation, and inhibiting cardiomyocyte apoptosis. Despite consistent preclinical efficacy, well-designed clinical trials are needed to validate its translational potential and safety in humans. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251168227, identifier CRD420251168227.