{"title":"Luteolin ameliorates ischemic/reperfusion injury by inhibiting ferroptosis.","authors":"Hua Li, Jin-Xia Li, Yi-di Zeng, Cai-Xing Zheng, Si-Si Dai, Jian Yi, Xu-Dong Song, Ting Liu, Wang-Hua Liu","doi":"10.1007/s11011-025-01588-9","DOIUrl":null,"url":null,"abstract":"<p><p>Ischaemic stroke is a large disease burden worldwide. Thrombolysis and thrombectomy are the main treatment methods for cerebral ischemia-reperfusion (I/R) injury. Luteolin, as a flavonoid compound, has an antagonistic effect on inflammation, oxidative stress, and tumorigenesis in disease. Therefore, the primary objective of this study is to determine the role of luteolin in cerebral I/R injury. Oxygen glucose deprivation/reoxygenation (OGD/R)-treated BV2 cells and a cerebral I/R rat model were established. Cell viability and death were verified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and propidium iodide staining. The glutathione/oxidized glutathione (GSH/GSSG) ratio, superoxide dismutase (SOD) activity, and reactive oxygen species (ROS) and malondialdehyde (MDA) levels were determined using corresponding kits. Solute Carrier Family 7 Member 11 (SLC7A11), nuclear transcription factor erythroid 2-related factor 2 (NRF2), and glutathione peroxidase 4 (GPX4) levels were analyzed by western blotting. In addition, the infarct volume of brain tissues was examined by tetrazolium chloride (TTC) staining. Luteolin treatment significantly enhanced cell viability, decreased LDH release and intracellular ROS and MDA levels, and increased the GSH/GSSG ratio and SOD activity in OGD/R-treated BV2 cells. PI staining demonstrated that cell death was inhibited after luteolin treatment. Additionally, luteolin treatment significantly increased the SLC7A11, NRF2, and GPX4 protein levels. After treatment with ML385, an NRF2 inhibitor, the influence of luteolin on OGD/R-treated BV2 cells was reversed. Moreover, luteolin treatment significantly decreased the neurological score and infarct area in the brain tissues of cerebral I/R rats. Our research demonstrated that luteolin treatment inhibited ferroptosis by enhancing antioxidant functions through the NRF2 pathway, which provides a promising method for treating cerebral I/R injury.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"159"},"PeriodicalIF":3.2000,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Metabolic brain disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11011-025-01588-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Ischaemic stroke is a large disease burden worldwide. Thrombolysis and thrombectomy are the main treatment methods for cerebral ischemia-reperfusion (I/R) injury. Luteolin, as a flavonoid compound, has an antagonistic effect on inflammation, oxidative stress, and tumorigenesis in disease. Therefore, the primary objective of this study is to determine the role of luteolin in cerebral I/R injury. Oxygen glucose deprivation/reoxygenation (OGD/R)-treated BV2 cells and a cerebral I/R rat model were established. Cell viability and death were verified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and propidium iodide staining. The glutathione/oxidized glutathione (GSH/GSSG) ratio, superoxide dismutase (SOD) activity, and reactive oxygen species (ROS) and malondialdehyde (MDA) levels were determined using corresponding kits. Solute Carrier Family 7 Member 11 (SLC7A11), nuclear transcription factor erythroid 2-related factor 2 (NRF2), and glutathione peroxidase 4 (GPX4) levels were analyzed by western blotting. In addition, the infarct volume of brain tissues was examined by tetrazolium chloride (TTC) staining. Luteolin treatment significantly enhanced cell viability, decreased LDH release and intracellular ROS and MDA levels, and increased the GSH/GSSG ratio and SOD activity in OGD/R-treated BV2 cells. PI staining demonstrated that cell death was inhibited after luteolin treatment. Additionally, luteolin treatment significantly increased the SLC7A11, NRF2, and GPX4 protein levels. After treatment with ML385, an NRF2 inhibitor, the influence of luteolin on OGD/R-treated BV2 cells was reversed. Moreover, luteolin treatment significantly decreased the neurological score and infarct area in the brain tissues of cerebral I/R rats. Our research demonstrated that luteolin treatment inhibited ferroptosis by enhancing antioxidant functions through the NRF2 pathway, which provides a promising method for treating cerebral I/R injury.
期刊介绍：
Metabolic Brain Disease serves as a forum for the publication of outstanding basic and clinical papers on all metabolic brain disease, including both human and animal studies. The journal publishes papers on the fundamental pathogenesis of these disorders and on related experimental and clinical techniques and methodologies. Metabolic Brain Disease is directed to physicians, neuroscientists, internists, psychiatrists, neurologists, pathologists, and others involved in the research and treatment of a broad range of metabolic brain disorders.
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