Flap transplantation is widely used in reconstructive surgery; however, ischemic injury remains a critical barrier to flap survival, primarily due to oxidative stress, ferroptosis, and impaired angiogenesis. In this study, we employed a random-pattern skin flap model in Sprague–Dawley rats to evaluate the protective effects of curcumin (Cur). Cur administration significantly enhanced antioxidant capacity by increasing superoxide dismutase (SOD) activity and heme oxygenase-1 (HO-1) expression while decreasing malondialdehyde (MDA) and lipid peroxidation (LPO) levels. Ferroptosis analysis revealed that Cur upregulated SLC7A11, GPX4, and FTH1 while downregulating ACSL4, indicating ferroptosis inhibition. Mechanistically, Cur activated the FoXO1/NCOA4 signaling pathway, suppressing NCOA4-mediated ferritinophagy and limiting iron-driven oxidative damage. Moreover, Cur promoted angiogenesis by upregulating VEGF, MMP9, and CDH5 and enhanced human umbilical vein endothelial cell (HUVEC) proliferation while reducing intracellular reactive oxygen species (ROS). Collectively, these findings demonstrate that Cur mitigates ischemic injury through antioxidative, antiferroptotic, and proangiogenic effects, supporting its therapeutic potential for improving flap survival in reconstructive surgery.
{"title":"Curcumin Mitigates Ischemic Damage in Flap Transplantation via Antioxidative, Antiferroptotic, and Proangiogenic Mechanisms","authors":"Xuejun Wu, Liang Guo, Yuning Li, Shibei Lin, Chu Chen","doi":"10.1155/ijcp/4773403","DOIUrl":"https://doi.org/10.1155/ijcp/4773403","url":null,"abstract":"<p>Flap transplantation is widely used in reconstructive surgery; however, ischemic injury remains a critical barrier to flap survival, primarily due to oxidative stress, ferroptosis, and impaired angiogenesis. In this study, we employed a random-pattern skin flap model in Sprague–Dawley rats to evaluate the protective effects of curcumin (Cur). Cur administration significantly enhanced antioxidant capacity by increasing superoxide dismutase (SOD) activity and heme oxygenase-1 (HO-1) expression while decreasing malondialdehyde (MDA) and lipid peroxidation (LPO) levels. Ferroptosis analysis revealed that Cur upregulated SLC7A11, GPX4, and FTH1 while downregulating ACSL4, indicating ferroptosis inhibition. Mechanistically, Cur activated the FoXO1/NCOA4 signaling pathway, suppressing NCOA4-mediated ferritinophagy and limiting iron-driven oxidative damage. Moreover, Cur promoted angiogenesis by upregulating VEGF, MMP9, and CDH5 and enhanced human umbilical vein endothelial cell (HUVEC) proliferation while reducing intracellular reactive oxygen species (ROS). Collectively, these findings demonstrate that Cur mitigates ischemic injury through antioxidative, antiferroptotic, and proangiogenic effects, supporting its therapeutic potential for improving flap survival in reconstructive surgery.</p>","PeriodicalId":13782,"journal":{"name":"International Journal of Clinical Practice","volume":"2025 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijcp/4773403","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145521440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}