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The recently discovered iron\u2010dependent mechanism of cell death known as ferroptosis has been linked to a wide range of pathologies. However, its role in iron overload\u2010induced retinal degeneration is still uncertain. Puerarin has been associated with retinal protection. The purpose of this research is to determine how puerarin prevents retinal ferroptosis under iron overload conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Models of iron overload in Kunming mice, 661W cell, and ARPE\u201019 cell are established. Increased iron deposition significantly worsens retinal pathology, decreases cell viability, and induces ferroptotic changes. Puerarin mitigates iron overload\u2010induced ferroptosis by decreasing excessive iron through the regulation of iron handling proteins and lowering lipid peroxidation through the inhibition of cyclooxygenase 2 expression and activation of the nuclear factor\u2010E2\u2010related factor 2 (Nrf2) signaling pathway and downstream ferroptosis\u2010related proteins (solute carrier family 7 member 11, glutathione peroxidase 4 and heme oxygenase\u20101). The protective effect of puerarin on ferroptosis is diminished by the Nrf2\u2010specific inhibitor ML385.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest targeting ferroptosis may be a novel strategy for the management of retinal degeneration. Puerarin may exert some of its ocular benefits by attenuating ferroptosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202300123","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T04:49:07Z","timestamp":1704862147000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Puerarin Attenuates Iron Overload\u2010Induced Ferroptosis in Retina through a Nrf2\u2010Mediated Mechanism"],"prefix":"10.1002","volume":"68","author":[{"given":"Qiongtao","family":"Song","sequence":"first","affiliation":[{"name":"Eye School of Chengdu University of TCM  No.37 Twelve Bridge Road Chengdu Sichuan 610075 China"},{"name":"Ineye Hospital of Chengdu University of TCM  No.8 Xinghui Road Chengdu Sichuan 610084 China"},{"name":"Key Laboratory of Sichuan Province Ophthalmopathy Prevention &amp; Cure and Visual Function Protection  No.37 Twelve Bridge Road Chengdu Sichuan 610075 China"},{"name":"Guangzhou Ineye Vision Health Innovation Institute  No.2 Fenghuang 3rd Road Guangzhou Guangdong 510555 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyuan","family":"Jian","sequence":"additional","affiliation":[{"name":"Eye School of Chengdu University of TCM  No.37 Twelve Bridge Road Chengdu Sichuan 610075 China"},{"name":"Ineye Hospital of Chengdu University of TCM  No.8 Xinghui Road Chengdu Sichuan 610084 China"},{"name":"Key Laboratory of Sichuan Province Ophthalmopathy Prevention &amp; 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