{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:05:19Z","timestamp":1791475519730,"version":"4.3.4"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82360790"],"award-info":[{"award-number":["82360790"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82360790"],"award-info":[{"award-number":["82360790"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009620","name":"Gansu Provincial Science and Technology Plan Project","doi-asserted-by":"publisher","award":["23JRRA1203"],"award-info":[{"award-number":["23JRRA1203"]}],"id":[{"id":"10.13039\/501100009620","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009620","name":"Gansu Provincial Science and Technology Plan Project","doi-asserted-by":"publisher","award":["23JR6KA028"],"award-info":[{"award-number":["23JR6KA028"]}],"id":[{"id":"10.13039\/501100009620","id-type":"DOI","asserted-by":"publisher"}]},{"award":["23JRRA1203"],"award-info":[{"award-number":["23JRRA1203"]}],"id":[{"id":"https:\/\/ror.org\/03xz2hx98","id-type":"ROR","asserted-by":"publisher"}]},{"award":["23JR6KA028"],"award-info":[{"award-number":["23JR6KA028"]}],"id":[{"id":"https:\/\/ror.org\/03xz2hx98","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: As a common clinical anticancer drug, doxorubicin (DOX) easily triggers obvious doxorubicin-induced cardiotoxicity (DIC) during clinical application. Accumulating evidence has proven that ferroptosis dominates the pathological process of DIC yet efficient targeted treatment strategies remain scarce. The present work mainly focused on clarifying the protective role of quercetin (QUE) against DIC. Methods: In vivo rat models and in vitro cardiomyocyte injury models were constructed to mimic DIC. Echocardiographic detection and histological staining were adopted to observe overall cardiac function and myocardial fibrotic changes. Ultrastructural alterations of intracellular mitochondria were observed under a transmission electron microscope. Relevant ferroptosis and oxidative stress levels were further determined. Moreover, a Western blot assay and NRF2 gene transfection technique were applied to confirm the involvement of the NRF2 signaling pathway. Results: In vivo and in vitro experimental outcomes showed that QUE treatment effectively relieved abnormal cardiac function and myocardial fibrotic lesions and improved damaged mitochondrial morphology. It also markedly restrained excessive iron accumulation and abnormal lipid peroxidation and restored disturbed redox balance in cardiomyocytes. Further mechanism exploration revealed that QUE could facilitate NRF2 entry into the cell nucleus and activate downstream SLC7A11\/GPX4 signaling to maintain cellular glutathione homeostasis. Silencing NRF2 expression could fully reverse the above beneficial influences of QUE. Conclusions: Collectively, our experimental data demonstrated that QUE confers cardioprotective effects against DIC within subacute rat models and cultured cardiomyocyte injury models. Further mechanistic observations revealed that this protective phenotype is closely linked to the activation of NRF2\/SLC7A11\/GPX4 signaling alongside obvious reductions in multiple characteristic ferroptosis markers.<\/jats:p>","DOI":"10.3390\/biom16081135","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:42:36Z","timestamp":1785850956000},"page":"1135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quercetin Activates NRF2\/SLC7A11\/GPX4 Signaling to Restore Mitochondrial Function Inhibit Ferroptosis Thereby Alleviating Doxorubicin-Induced Cardiotoxicity"],"prefix":"10.3390","volume":"16","author":[{"given":"Jialong","family":"Liu","sequence":"first","affiliation":[{"name":"School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zirong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafang","family":"Qi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongling","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"},{"name":"Northwest Collaborative Innovation Center for Traditional Chinese Medicine, Lanzhou 730000, China"},{"name":"Gansu Pharmaceutical Industry Innovation Research Institute, Gansu University of Chinese Medicine, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Law, D., Magrini, M.A., Siedlik, J.A., Eckerson, J., Drescher, K.M., and Bredahl, E.C. 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