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Alliance"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>Ferroptosis is triggered by the breakdown of cellular iron-dependent redox homeostasis and the abnormal accumulation of lipid ROS. Cells have evolved defense mechanisms to prevent lipid ROS accumulation and ferroptosis. Using a library of more than 4,000 bioactive compounds, we show that tanshinone from<jats:italic>Salvia miltiorrhiza<\/jats:italic>(Danshen) has very potent inhibitory activity against ferroptosis. Mechanistically, we found that tanshinone functions as a coenzyme for NAD(P)H:quinone oxidoreductase 1 (NQO1), which detoxifies lipid peroxyl radicals and inhibits ferroptosis both in vitro and in vivo. Although NQO1 is recognized as an oxidative stress response gene, it does not appear to have a direct role in ferroptosis inhibition in the absence of tanshinone. Here, we demonstrate a gain of function of NQO1 induced by tanshinone, which is a novel mechanism for ferroptosis inhibition. Using mouse models of acute liver injury and ischemia\/reperfusion heart injury, we observed that tanshinone displays protective effects in both the liver and the heart in a manner dependent on NQO1. Our results link the clinical use of tanshinone to its activity in ferroptosis inhibition.<\/jats:p>","DOI":"10.26508\/lsa.202201667","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T15:35:13Z","timestamp":1667316913000},"page":"e202201667","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":46,"title":["Tanshinone functions as a coenzyme that confers gain of function of NQO1 to suppress ferroptosis"],"prefix":"10.26508","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5215-830X","authenticated-orcid":true,"given":"Tian-Xiang","family":"Wang","sequence":"first","affiliation":[{"name":"The Fifth People\u2019s Hospital of Shanghai, The Molecular and Cell Biology Research Lab of the Institutes of Biomedical Sciences and the School of Pharmacy, Fudan University, Shanghai, 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