{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:26:15Z","timestamp":1789043175584,"version":"build-2803163510"},"reference-count":117,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T00:00:00Z","timestamp":1726185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Shandong Province","award":["ZR2021QH166"],"award-info":[{"award-number":["ZR2021QH166"]}]},{"name":"Talent Induction Program for Youth Innovation Teams in Colleges and Universities of Shandong Province","award":["ZR2021QH166"],"award-info":[{"award-number":["ZR2021QH166"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Stroke is a severe neurological disorder resulting from the rupture or blockage of blood vessels, leading to significant mortality and disability worldwide. Among the different types of stroke, ischemic stroke (IS) is the most prevalent, accounting for 70\u201380% of cases. Cell death following IS occurs through various mechanisms, including apoptosis, necrosis, and ferroptosis. Ferroptosis, a recently identified form of regulated cell death characterized by iron overload and lipid peroxidation, was first described by Dixon in 2012. Currently, the only approved pharmacological treatment for IS is recombinant tissue plasminogen activator (rt-PA), which is limited by a narrow therapeutic window and often results in suboptimal outcomes. Recent research has identified several traditional Chinese medicines (TCMs) that can inhibit ferroptosis, thereby mitigating the damage caused by IS. This review provides an overview of stroke, the role of ferroptosis in IS, and the potential of certain TCMs to inhibit ferroptosis and contribute to stroke treatment.<\/jats:p>","DOI":"10.3390\/molecules29184359","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T08:45:53Z","timestamp":1726217153000},"page":"4359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Ferroptosis in Ischemic Stroke and Related Traditional Chinese Medicines"],"prefix":"10.3390","volume":"29","author":[{"given":"Runchen","family":"Ma","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9995-0589","authenticated-orcid":false,"given":"Xiaohui","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaofeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6030-3570","authenticated-orcid":false,"given":"Gangqiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Tian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,13]]},"reference":[{"key":"ref_1","first-page":"33","article-title":"China stroke surveillance report 2021","volume":"10","author":"Tu","year":"2023","journal-title":"Mil. Med. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1159\/000210432","article-title":"Classification of stroke subtypes","volume":"27","author":"Amarenco","year":"2009","journal-title":"Cerebrovasc. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1212\/WNL.0000000000012781","article-title":"Global Epidemiology of Stroke and Access to Acute Ischemic Stroke Interventions","volume":"97","author":"Saini","year":"2021","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1136\/svn-2021-001374","article-title":"China Stroke Statistics: An update on the 2019 report from the National Center for Healthcare Quality Management in Neurological Diseases, China National Clinical Research Center for Neurological Diseases, the Chinese Stroke Association, National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention and Institute for Global Neuroscience and Stroke Collaborations","volume":"7","author":"Wang","year":"2022","journal-title":"Stroke Vasc. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/med.21817","article-title":"Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications","volume":"42","author":"Tuo","year":"2022","journal-title":"Med. Res. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1097\/CCM.0000000000004597","article-title":"Management of Acute Ischemic Stroke","volume":"48","author":"Herpich","year":"2020","journal-title":"Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1001\/jama.2020.26867","article-title":"Diagnosis and Management of Transient Ischemic Attack and Acute Ischemic Stroke: A Review","volume":"325","author":"Mendelson","year":"2021","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/j.amjmed.2021.07.027","article-title":"Ischemic Stroke","volume":"134","author":"Feske","year":"2021","journal-title":"Am. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3892\/ijmm.2021.5070","article-title":"Neuronal injuries in cerebral infarction and ischemic stroke: From mechanisms to treatment (Review)","volume":"49","author":"Zhao","year":"2022","journal-title":"Int. J. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/nm.2507","article-title":"Ischemia and reperfusion--from mechanism to translation","volume":"17","author":"Eltzschig","year":"2011","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41392-022-01064-1","article-title":"Signaling pathways involved in ischemic stroke: Molecular mechanisms and therapeutic interventions","volume":"7","author":"Qin","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1080\/15548627.2020.1810918","article-title":"Ferroptosis: Machinery and regulation","volume":"17","author":"Chen","year":"2021","journal-title":"Autophagy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1084\/jem.102.1.37","article-title":"The specific amino acid requirements of a human carcinoma cell (Stain HeLa) in tissue culture","volume":"102","author":"Eagle","year":"1955","journal-title":"J. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1126\/science.130.3373.432","article-title":"Amino acid metabolism in mammalian cell cultures","volume":"130","author":"Eagle","year":"1959","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.cmet.2020.10.011","article-title":"The Metabolic Underpinnings of Ferroptosis","volume":"32","author":"Zheng","year":"2020","journal-title":"Cell Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/0005-2760(82)90150-3","article-title":"Purification from pig liver of a protein which protects liposomes and biomembranes from peroxidative degradation and exhibits glutathione peroxidase activity on phosphatidylcholine hydroperoxides","volume":"710","author":"Ursini","year":"1982","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S1474-4422(18)30500-3","article-title":"Stroke in China: Advances and challenges in epidemiology, prevention, and management","volume":"18","author":"Wu","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_20","first-page":"3238165","article-title":"Stroke in the 21(st) Century: A Snapshot of the Burden, Epidemiology, and Quality of Life","volume":"2018","author":"Donkor","year":"2018","journal-title":"Stroke Res. Treat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1161\/STR.0b013e31829734f2","article-title":"Forecasting the future of stroke in the United States: A policy statement from the American Heart Association and American Stroke Association","volume":"44","author":"Ovbiagele","year":"2013","journal-title":"Stroke"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.mpmed.2020.06.002","article-title":"Stroke: Causes and clinical features","volume":"48","author":"Murphy","year":"2020","journal-title":"Medicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1007\/s12017-019-08530-0","article-title":"Blood Biomarkers for Stroke Diagnosis and Management","volume":"21","author":"Jickling","year":"2019","journal-title":"NeuroMol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1161\/01.STR.0000258355.23810.c6","article-title":"Outcomes validity and reliability of the modified Rankin scale: Implications for stroke clinical trials: A literature review and synthesis","volume":"38","author":"Banks","year":"2007","journal-title":"Stroke"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.jcin.2015.11.014","article-title":"Endovascular Reperfusion Strategies for Acute Stroke","volume":"9","author":"Papanagiotou","year":"2016","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41419-020-2298-2","article-title":"Ferroptosis: Past, present and future","volume":"11","author":"Li","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Han, C., Liu, Y., Dai, R., Ismail, N., Su, W., and Li, B. (2020). Ferroptosis and Its Potential Role in Human Diseases. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00239"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/jnc.15807","article-title":"Iron, ferroptosis, and ischemic stroke","volume":"165","author":"Guo","year":"2023","journal-title":"J. Neurochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41422-020-00441-1","article-title":"Ferroptosis: Molecular mechanisms and health implications","volume":"31","author":"Tang","year":"2021","journal-title":"Cell Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nchembio.2238","article-title":"Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis","volume":"13","author":"Kagan","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5866","DOI":"10.1021\/cr200246d","article-title":"Lipoxygenase and leukotriene pathways: Biochemistry, biology, and roles in disease","volume":"111","author":"Haeggstrom","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1146\/annurev-nutr-062320-112625","article-title":"Molecular Mechanisms of Iron and Heme Metabolism","volume":"42","author":"Dutt","year":"2022","journal-title":"Annu. Rev. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nchembio.1416","article-title":"The role of iron and reactive oxygen species in cell death","volume":"10","author":"Dixon","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: Mechanisms, biology and role in disease","volume":"22","author":"Jiang","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"R1292","DOI":"10.1016\/j.cub.2020.09.068","article-title":"Ferroptosis","volume":"30","author":"Tang","year":"2020","journal-title":"Curr. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1038\/s41418-020-00728-1","article-title":"Cellular degradation systems in ferroptosis","volume":"28","author":"Chen","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1046\/j.1471-4159.2001.00385.x","article-title":"Dibutyryl-cAMP (dbcAMP) up-regulates astrocytic chloride-dependent L-[3H]glutamate transport and expression of both system xc(-) subunits","volume":"78","author":"Gochenauer","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"108373","DOI":"10.1016\/j.pharmthera.2023.108373","article-title":"Molecular mechanisms of ferroptosis and their involvement in brain diseases","volume":"244","author":"Costa","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Belalcazar, A.D., Ball, J.G., Frost, L.M., Valentovic, M.A., and Wilkinson, J. (2014). Transsulfuration Is a Significant Source of Sulfur for Glutathione Production in Human Mammary Epithelial Cells. ISRN Biochem., 2013.","DOI":"10.1155\/2013\/637897"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"37423","DOI":"10.1074\/jbc.M506439200","article-title":"Redox imbalance in cystine\/glutamate transporter-deficient mice","volume":"280","author":"Sato","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.tcb.2015.12.007","article-title":"Understanding Ubiquinone","volume":"26","author":"Wang","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.freeradbiomed.2021.02.039","article-title":"The multiple roles of coenzyme Q in cellular homeostasis and their relevance for the pathogenesis of coenzyme Q deficiency","volume":"166","author":"Baschiera","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1038\/s41467-022-29905-1","article-title":"A targetable CoQ-FSP1 axis drives ferroptosis- and radiation-resistance in KEAP1 inactive lung cancers","volume":"13","author":"Koppula","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/s41586-019-1705-2","article-title":"The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis","volume":"575","author":"Bersuker","year":"2019","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8832043","DOI":"10.1155\/2020\/8832043","article-title":"Posttranslational Modifications in Ferroptosis","volume":"2020","author":"Wei","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1021\/acscentsci.9b01063","article-title":"GTP Cyclohydrolase 1\/Tetrahydrobiopterin Counteract Ferroptosis through Lipid Remodeling","volume":"6","author":"Kraft","year":"2020","journal-title":"ACS Cent. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s41422-022-00642-w","article-title":"The structure of erastin-bound xCT-4F2hc complex reveals molecular mechanisms underlying erastin-induced ferroptosis","volume":"32","author":"Yan","year":"2022","journal-title":"Cell Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.chembiol.2019.01.008","article-title":"Imidazole Ketone Erastin Induces Ferroptosis and Slows Tumor Growth in a Mouse Lymphoma Model","volume":"26","author":"Zhang","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e02523","DOI":"10.7554\/eLife.02523","article-title":"Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis","volume":"3","author":"Dixon","year":"2014","journal-title":"eLife"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1172\/JCI992","article-title":"Sulfasalazine: A potent and specific inhibitor of nuclear factor kappa B","volume":"101","author":"Wahl","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1038\/sj.leu.2402238","article-title":"Sulfasalazine, a potent suppressor of lymphoma growth by inhibition of the x(c)- cystine transporter: A new action for an old drug","volume":"15","author":"Gout","year":"2001","journal-title":"Leukemia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1089\/ars.2011.4391","article-title":"The cystine\/glutamate antiporter system x(c)(-) in health and disease: From molecular mechanisms to novel therapeutic opportunities","volume":"18","author":"Lewerenz","year":"2013","journal-title":"Antioxid. Redox Signal"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/s41418-017-0053-8","article-title":"miR-137 regulates ferroptosis by targeting glutamine transporter SLC1A5 in melanoma","volume":"25","author":"Luo","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/s41420-023-01475-1","article-title":"alpha-KG inhibits tumor growth of diffuse large B-cell lymphoma by inducing ROS and TP53-mediated ferroptosis","volume":"9","author":"Cai","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.chembiol.2008.02.010","article-title":"Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells","volume":"15","author":"Yang","year":"2008","journal-title":"Chem. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"E4966","DOI":"10.1073\/pnas.1603244113","article-title":"Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis","volume":"113","author":"Yang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"8279851","DOI":"10.1155\/2022\/8279851","article-title":"Pomelo Peel Essential Oil Ameliorates Cerebral Ischemia-Reperfusion Injury through Regulating Redox Homeostasis in Rats and SH-SY5Y Cells","volume":"2022","author":"Hu","year":"2022","journal-title":"Oxidative Med. Cell Longev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1016\/j.bmcl.2011.09.047","article-title":"Development of small-molecule probes that selectively kill cells induced to express mutant RAS","volume":"22","author":"Weiwer","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-019-1170-y","article-title":"CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy","volume":"569","author":"Wang","year":"2019","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Faraji, P., Borchert, A., Ahmadian, S., and Kuhn, H. (2024). Butylated Hydroxytoluene (BHT) Protects SH-SY5Y Neuroblastoma Cells from Ferroptotic Cell Death: Insights from In Vitro and In Vivo Studies. Antioxidants, 13.","DOI":"10.3390\/antiox13020242"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10036","DOI":"10.1021\/acs.jmedchem.3c00967","article-title":"Discovery of Novel Potent Covalent Glutathione Peroxidase 4 Inhibitors as Highly Selective Ferroptosis Inducers for the Treatment of Triple-Negative Breast Cancer","volume":"66","author":"Chen","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e1904197","DOI":"10.1002\/adma.201904197","article-title":"Recent Progress in Ferroptosis Inducers for Cancer Therapy","volume":"31","author":"Liang","year":"2019","journal-title":"Adv. Mater."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/nchembio.2079","article-title":"Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis","volume":"12","author":"Shimada","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/s41419-021-04306-2","article-title":"Fin56-induced ferroptosis is supported by autophagy-mediated GPX4 degradation and functions synergistically with mTOR inhibition to kill bladder cancer cells","volume":"12","author":"Sun","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1021\/acschembio.5b00900","article-title":"Five-Membered Ring Peroxide Selectively Initiates Ferroptosis in Cancer Cells","volume":"11","author":"Abrams","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/s41589-018-0031-6","article-title":"FINO(2) initiates ferroptosis through GPX4 inactivation and iron oxidation","volume":"14","author":"Gaschler","year":"2018","journal-title":"Nat. Chem. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Miotto, G., Rossetto, M., Di Paolo, M.L., Orian, L., Venerando, R., Roveri, A., Vuckovic, A.M., Bosello Travain, V., Zaccarin, M., and Zennaro, L. (2020). Insight into the mechanism of ferroptosis inhibition by ferrostatin-1. Redox Biol., 28.","DOI":"10.1016\/j.redox.2019.101328"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"528","DOI":"10.4103\/1673-5374.266060","article-title":"Ferrostatin-1 protects HT-22 cells from oxidative toxicity","volume":"15","author":"Chu","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1021\/acscentsci.7b00028","article-title":"On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death","volume":"3","author":"Zilka","year":"2017","journal-title":"ACS Cent. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/ncb3064","article-title":"Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice","volume":"16","author":"Schneider","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1126\/science.56.1458.650","article-title":"On the Existence of a Hitherto Unrecognized Dietary Factor Essential for Reproduction","volume":"56","author":"Evans","year":"1922","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.pharmthera.2015.12.003","article-title":"Vitamin E therapy beyond cancer: Tocopherol versus tocotrienol","volume":"162","author":"Peh","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.freeradbiomed.2021.08.234","article-title":"Diverse cytoprotective actions of vitamin E isoforms\u2014role as peroxyl radical scavengers and complementary functions with selenoproteins","volume":"175","author":"Saito","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/mnfr.200900439","article-title":"The location and behavior of alpha-tocopherol in membranes","volume":"54","author":"Atkinson","year":"2010","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.tips.2023.08.012","article-title":"Beyond ferrostatin-1: A comprehensive review of ferroptosis inhibitors","volume":"44","author":"Scarpellini","year":"2023","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0098-2997(92)90013-P","article-title":"Iron chelators in medicine","volume":"13","author":"Hershko","year":"1992","journal-title":"Mol. Asp. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1093\/humrep\/deaa363","article-title":"Erastin induces ferroptosis via ferroportin-mediated iron accumulation in endometriosis","volume":"36","author":"Li","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Guo, Z., Lin, J., Sun, K., Guo, J., Yao, X., Wang, G., Hou, L., Xu, J., Guo, J., and Guo, F. (2022). Deferoxamine Alleviates Osteoarthritis by Inhibiting Chondrocyte Ferroptosis and Activating the Nrf2 Pathway. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.791376"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e13158","DOI":"10.1111\/cpr.13158","article-title":"Sorafenib attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis via HIF-1alpha\/SLC7A11 pathway","volume":"55","author":"Yuan","year":"2022","journal-title":"Cell Prolif."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0140-6736(85)91472-2","article-title":"New orally active iron chelators","volume":"1","author":"Kontoghiorghes","year":"1985","journal-title":"Lancet"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Kontoghiorghes, G.J. (2022). Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126735"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41418-022-01046-4","article-title":"Pathologically high intraocular pressure disturbs normal iron homeostasis and leads to retinal ganglion cell ferroptosis in glaucoma","volume":"30","author":"Yao","year":"2023","journal-title":"Cell Death Differ."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.stem.2019.09.003","article-title":"Oligodendrocyte Death in Pelizaeus-Merzbacher Disease Is Rescued by Iron Chelation","volume":"25","author":"Nobuta","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"154112","DOI":"10.1016\/j.phymed.2022.154112","article-title":"beta-Caryophyllene suppresses ferroptosis induced by cerebral ischemia reperfusion via activation of the NRF2\/HO-1 signaling pathway in MCAO\/R rats","volume":"102","author":"Hu","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cbi.2016.11.015","article-title":"The cannabinoid beta-caryophyllene (BCP) induces neuritogenesis in PC12 cells by a cannabinoid-receptor-independent mechanism","volume":"261","author":"Santos","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2174\/1871527321666220324115848","article-title":"The Protective Effect of Vitexin Compound B-1 on Rat Cerebral I\/R Injury through a Mechanism Involving Modulation of miR-92b\/NOX4 Pathway","volume":"22","author":"Hu","year":"2023","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1007\/s11064-022-03829-0","article-title":"Vitexin Improves Cerebral ischemia\u2014reperfusion Injury by Attenuating Oxidative Injury and Ferroptosis via Keap1\/Nrf2\/HO-1signaling","volume":"48","author":"Guo","year":"2023","journal-title":"Neurochem. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1080\/10520295.2021.1937701","article-title":"A review of the protective effects of quercetin-rich natural compounds for treating ischemia-reperfusion injury","volume":"97","author":"Javadinia","year":"2022","journal-title":"Biotech. Histochem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1080\/10286020.2021.1949302","article-title":"Quercetin attenuates ischemia reperfusion injury by protecting the blood-brain barrier through Sirt1 in MCAO rats","volume":"24","author":"Yang","year":"2022","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jinorgbio.2011.11.014","article-title":"Quercetin as a shuttle for labile iron","volume":"107","author":"Baccan","year":"2012","journal-title":"J. Inorg. Biochem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"176264","DOI":"10.1016\/j.ejphar.2023.176264","article-title":"Quercetin attenuates cerebral ischemic injury by inhibiting ferroptosis via Nrf2\/HO-1 signaling pathway","volume":"963","author":"Peng","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"114541","DOI":"10.1016\/j.expneurol.2023.114541","article-title":"Rhein attenuates cerebral ischemia-reperfusion injury via inhibition of ferroptosis through NRF2\/SLC7A11\/GPX4 pathway","volume":"369","author":"Liu","year":"2023","journal-title":"Exp. Neurol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Li, Y., Zhang, E., Yang, H., Chen, Y., Tao, L., Xu, Y., Chen, T., and Shen, X. (2022). Gastrodin Ameliorates Cognitive Dysfunction in Vascular Dementia Rats by Suppressing Ferroptosis via the Regulation of the Nrf2\/Keap1-GPx4 Signaling Pathway. Molecules, 27.","DOI":"10.3390\/molecules27196311"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"104715","DOI":"10.1016\/j.tiv.2019.104715","article-title":"Gastrodin protects against glutamate-induced ferroptosis in HT-22 cells through Nrf2\/HO-1 signaling pathway","volume":"62","author":"Jiang","year":"2020","journal-title":"Toxicol. in Vitro"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e14456","DOI":"10.1111\/cns.14456","article-title":"Neutral polysaccharide from Gastrodia elata alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis-mediated neuroinflammation via the NRF2\/HO-1 signaling pathway","volume":"30","author":"Zhang","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"154729","DOI":"10.1016\/j.phymed.2023.154729","article-title":"Loureirin C inhibits ferroptosis after cerebral ischemia reperfusion through regulation of the Nrf2 pathway in mice","volume":"113","author":"Liu","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/bph.15961","article-title":"Icariside II preconditioning evokes robust neuroprotection against ischaemic stroke, by targeting Nrf2 and the OXPHOS\/NF-kappaB\/ferroptosis pathway","volume":"180","author":"Gao","year":"2023","journal-title":"Br. J. Pharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.biopha.2018.04.005","article-title":"Icariside II alleviates oxygen-glucose deprivation and reoxygenation-induced PC12 cell oxidative injury by activating Nrf2\/SIRT3 signaling pathway","volume":"103","author":"Feng","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/fcp.12232","article-title":"Research review on the pharmacological effects of astragaloside IV","volume":"31","author":"Li","year":"2017","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"175516","DOI":"10.1016\/j.ejphar.2023.175516","article-title":"Astragaloside IV mitigates cerebral ischaemia-reperfusion injury via inhibition of P62\/Keap1\/Nrf2 pathway-mediated ferroptosis","volume":"944","author":"Wang","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"115021","DOI":"10.1016\/j.jep.2022.115021","article-title":"Rehmannioside A improves cognitive impairment and alleviates ferroptosis via activating PI3K\/AKT\/Nrf2 and SLC7A11\/GPX4 signaling pathway after ischemia","volume":"289","author":"Fu","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_103","first-page":"163","article-title":"Salvia miltiorrhiza: Traditional medicinal uses, chemistry, and pharmacology","volume":"13","author":"Su","year":"2015","journal-title":"Chin. J. Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"154790","DOI":"10.1016\/j.phymed.2023.154790","article-title":"15, 16-Dihydrotanshinone I protects against ischemic stroke by inhibiting ferroptosis via the activation of nuclear factor erythroid 2-related factor 2","volume":"114","author":"Wu","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_105","unstructured":"Dihydromyricetin (2012). LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, National Institute of Diabetes and Digestive and Kidney Diseases."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.2147\/DDDT.S378786","article-title":"Dihydromyricetin Attenuates Cerebral Ischemia Reperfusion Injury by Inhibiting SPHK1\/mTOR Signaling and Targeting Ferroptosis","volume":"16","author":"Xie","year":"2022","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Li, M., Meng, Z., Yu, S., Li, J., Wang, Y., Yang, W., and Wu, H. (2022). Baicalein ameliorates cerebral ischemia-reperfusion injury by inhibiting ferroptosis via regulating GPX4\/ACSL4\/ACSL3 axis. Chem. Biol. Interact., 366.","DOI":"10.1016\/j.cbi.2022.110137"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"118660","DOI":"10.1016\/j.lfs.2020.118660","article-title":"Galangin attenuated cerebral ischemia-reperfusion injury by inhibition of ferroptosis through activating the SLC7A11\/GPX4 axis in gerbils","volume":"264","author":"Guan","year":"2021","journal-title":"Life Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.joim.2020.01.008","article-title":"Extract of Naotaifang, a compound Chinese herbal medicine, protects neuron ferroptosis induced by acute cerebral ischemia in rats","volume":"18","author":"Lan","year":"2020","journal-title":"J. Integr. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"117657","DOI":"10.1016\/j.jep.2023.117657","article-title":"Danlou tablet attenuates ischemic stroke injury and blood\u2014brain barrier damage by inhibiting ferroptosis","volume":"322","author":"Liu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"115836","DOI":"10.1016\/j.jep.2022.115836","article-title":"Protective effect of Xingnaojing injection on ferroptosis after cerebral ischemia injury in MCAO rats and SH-SY5Y cells","volume":"301","author":"Liu","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s12035-022-03075-z","article-title":"SATB1\/SLC7A11\/HO-1 Axis Ameliorates Ferroptosis in Neuron Cells After Ischemic Stroke by Danhong Injection","volume":"60","author":"Zhan","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"346918","DOI":"10.1155\/2014\/346918","article-title":"Use of angong niuhuang in treating central nervous system diseases and related research","volume":"2014","author":"Guo","year":"2014","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Tsoi, B., Chen, X., Gao, C., Wang, S., Yuen, S.C., Yang, D., and Shen, J. (2019). Neuroprotective Effects and Hepatorenal Toxicity of Angong Niuhuang Wan Against Ischemia-Reperfusion Brain Injury in Rats. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00593"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"117438","DOI":"10.1016\/j.jep.2023.117438","article-title":"Angong Niuhuang Wan inhibit ferroptosis on ischemic and hemorrhagic stroke by activating PPARgamma\/AKT\/GPX4 pathway","volume":"321","author":"Bai","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"He, D.Y., and Dai, S.M. (2011). Anti-inflammatory and immunomodulatory effects of paeonia lactiflora pall. a traditional chinese herbal medicine. Front. Pharmacol., 2.","DOI":"10.3389\/fphar.2011.00010"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"116567","DOI":"10.1016\/j.jep.2023.116567","article-title":"Paeoniae Radix Rubra extract attenuates cerebral ischemia injury by inhibiting ferroptosis and activating autophagy through the PI3K\/Akt signalling pathway","volume":"315","author":"Zhao","year":"2023","journal-title":"J. Ethnopharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/18\/4359\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:55:47Z","timestamp":1760111747000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/18\/4359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,13]]},"references-count":117,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["molecules29184359"],"URL":"https:\/\/doi.org\/10.3390\/molecules29184359","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,13]]}}}