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This narrative review systematically synthesizes current evidence on the protective efficacy and molecular mechanisms of curcumin, a natural polyphenolic compound, against ischemia\u2013reperfusion injury across major organ systems. Mechanistically, curcumin orchestrates a multitargeted defense by activating the nuclear factor erythroid 2-related factor 2\/heme oxygenase-1 antioxidant axis, suppressing the nuclear factor kappa-light-chain-enhancer of activated B cells-driven inflammatory storm, and modulating the phosphoinositide 3-kinase\/protein kinase B survival pathway. These actions collectively result in the inhibition of reactive oxygen species generation, mitigation of mitochondria-dependent apoptosis, and preservation of microcirculatory integrity. Although curcumin demonstrates significant protective effects across the heart, liver, kidneys, lungs, brain, spinal cord, and intestines by reducing tissue damage markers and ameliorating pathological morphology, its clinical translation remains hindered by the inherent drawbacks of poor water solubility, low oral bioavailability, and rapid metabolic clearance. Future research should prioritize the integration of curcumin with advanced nanocarrier delivery systems and high-resolution spatial transcriptomics to enhance targeted therapeutic efficacy, thereby paving the way for novel clinical strategies against ischemia\u2013reperfusion injury.<\/jats:p>","DOI":"10.1177\/03000605261480957","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T12:00:02Z","timestamp":1787832002000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Curcumin in ischemia\u2013reperfusion injury across multiple organs: A review"],"prefix":"10.1177","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6225-1225","authenticated-orcid":false,"given":"Jun","family":"Lu","sequence":"first","affiliation":[{"name":"School of Medicine, Affiliated Hangzhou First People's Hospital, Westlake University"},{"name":"Zhejiang University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixi","family":"Fang","sequence":"additional","affiliation":[{"name":"School of Medicine, Affiliated Hangzhou First People's Hospital, Westlake University"},{"name":"School of Medicine, Hangzhou Normal University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyong","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Medicine, Affiliated Hangzhou First People's Hospital, Westlake University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9045-7973","authenticated-orcid":false,"given":"Xiao","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhejiang University"},{"name":"Hepatobiliary Center and Transplantation Center, The First Affiliated Hospital with Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01688-x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.11.010"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60126-X"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s41073-019-0064-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2507"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394309-5.00006-7"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000489241"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-0403-y"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hjc.2018.11.002"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200106000-00030"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03579.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.06.017"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45161"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62874"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70136"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200207-670SO"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/10790268.2020.1737788"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2025.07.061"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.acvd.2016.05.005"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1113\/EP087122"},{"key":"e_1_3_3_22_2","article-title":"Magnetically-Induced suppression of oxidative stress prevents venous thrombosis","volume":"13","author":"Zhang NN","year":"2026","unstructured":"Zhang NN, An YR, Tao SR, et al. 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