{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:55:27Z","timestamp":1785412527281,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Youth Science and Technology Innovation Talent Cultivation Program of FJTCM","award":["XQB202201"],"award-info":[{"award-number":["XQB202201"]}]},{"name":"Scientific Research Foundation for the High-level Talents, Fujian University of Traditional Chinese Medicine","award":["X2021003-talent"],"award-info":[{"award-number":["X2021003-talent"]}]},{"name":"Scientific Research Foundation for the High-level Talents, Fujian University of Traditional Chinese Medicine","award":["X2024001-talent"],"award-info":[{"award-number":["X2024001-talent"]}]},{"name":"Scientific Research Foundation for the High-level Talents, Fujian University of Traditional Chinese Medicine","award":["X2024009-talent"],"award-info":[{"award-number":["X2024009-talent"]}]},{"award":["X2021003-talent"],"award-info":[{"award-number":["X2021003-talent"]}],"id":[{"id":"https:\/\/ror.org\/05n0qbd70","id-type":"ROR","asserted-by":"publisher"}]},{"award":["X2024001-talent"],"award-info":[{"award-number":["X2024001-talent"]}],"id":[{"id":"https:\/\/ror.org\/05n0qbd70","id-type":"ROR","asserted-by":"publisher"}]},{"award":["X2024009-talent"],"award-info":[{"award-number":["X2024009-talent"]}],"id":[{"id":"https:\/\/ror.org\/05n0qbd70","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Myocardial infarction (MI) remains the leading cause of death globally. Current treatment strategies involve restoring blood flow to the coronary artery, but have shortcomings in that these procedures cannot reverse damage to the myocardium that has already occurred. Therefore, therapies that can decrease the severity of ischemic damage are needed. Oxidative stress is an early and major driver of cardiomyocyte death following MI. Rhynchophylline (RHY) is a natural alkaloid known for its antioxidant activity; however, whether it can protect against MI-induced ischemic injury, as well as its underlying mechanism of action, remains unexplored. We performed murine models of surgical MI and examined the effects and mechanisms of RHY in protecting against myocardial ischemic injury. A sirtuin 1 (SIRT1)-specific inhibitor, EX-527, was subsequently used to verify that the cardioprotective effects of RHY were dependent upon targeted SIRT1-activation. Mice administered with RHY significantly protected against ischemic injury following MI, with improved cardiac function, reduced infarct size, and decreased levels of oxidative and DNA damage. The cardioprotective effect of RHY is associated with activation of the SIRT1 and its downstream redox-sensitive transcription factors: nuclear factor erythroid 2-related factor 2 (NRF2) and forkhead-box protein O3 (FOXO3a). The cardioprotective and antioxidant effects of RHY were abolished by EX-527, a selective SIRT1 inhibitor. Our findings provide evidence for the robust antioxidant properties of RHY in protecting against MI injury via activating the SIRT1\/NRF2\/FOXO3a signaling axis. These findings provide new mechanistic insight into the preconditioning-like cardioprotective potential of RHY during myocardial infarction.<\/jats:p>","DOI":"10.3390\/antiox15060669","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T16:17:58Z","timestamp":1779812278000},"page":"669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rhynchophylline Protects Against Ischemic Injury Following Myocardial Infarction via Activation of the SIRT1\/NRF2\/FOXO3a Axis"],"prefix":"10.3390","volume":"15","author":[{"given":"Wenyue","family":"Yang","sequence":"first","affiliation":[{"name":"Academy of Integrative Medicine, College of Integrative Medicine, Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En","family":"Ma","sequence":"additional","affiliation":[{"name":"Academy of Integrative Medicine, College of Integrative Medicine, Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Academy of Integrative Medicine, College of Integrative Medicine, Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Yang","sequence":"additional","affiliation":[{"name":"Academy of Integrative Medicine, College of Integrative Medicine, Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Academy of Integrative Medicine, College of Integrative Medicine, Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Academy of Integrative Medicine, College of Integrative Medicine, Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7431-8156","authenticated-orcid":false,"given":"Dan-ni","family":"Ren","sequence":"additional","affiliation":[{"name":"Academy of Integrative Medicine, College of Integrative Medicine, Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8577-7729","authenticated-orcid":false,"given":"Da","family":"Wo","sequence":"additional","affiliation":[{"name":"Academy of Integrative Medicine, College of Integrative Medicine, Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"ref_1","first-page":"e41","article-title":"2025 heart disease and stroke statistics: A report of US and global data from the American heart association","volume":"151","author":"Martin","year":"2025","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1016\/S0140-6736(21)02334-5","article-title":"Percutaneous coronary intervention with drug-eluting stents versus coronary artery bypass grafting in left main coronary artery disease: An individual patient data meta-analysis","volume":"398","author":"Sabatine","year":"2021","journal-title":"Lancet"},{"key":"ref_3","first-page":"935","article-title":"Targeting reperfusion injury in patients with ST-segment elevation myocardial infarction: Trials and tribulations","volume":"38","author":"Hausenloy","year":"2017","journal-title":"Eur. 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