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This study investigates the ferroptosis mechanism of XLCQD against cerebral ischemia\/reperfusion (I\/R) injury using rat models of middle cerebral artery occlusion\/reperfusion (MCAO\/R). Ferroptosis differs from traditional cell death pathways and is linked to oxidative stress\u2010induced lipid peroxidation and glutathione (GSH) depletion, which is essential to the development of ischemic stroke. In this study, it is shown that XLCQD improves brain infarction, neurological dysfunction, and histopathological changes caused by MCAO\/R exposure, and improving I\/R\u2010induced oxidative damage through inhibition of ferroptosis via (Solute Carrier Family 7 Member 11) SLC7A11\/ (glutathione peroxidase 4) GPX4 pathway. Interestingly, it is found that XLCQD\u2010mediated protection in I\/R\u00a0is reversed by the silence of SLC7A11. XLCQD intervention significantly promotes GSH content and suppresses Reactive Oxygen Species(ROS), iron accumulation, as well as Malondialdehyde (MDA) generation, are markedly abrogated when SLC7A11 is knockdown by SLC7A11\u2010shRNA transfection, indicating that SLC7A11 is the main target of XLCQD to further trigger intracellular events. In conclusion, XLCQD attenuates in vivo cerebral I\/R injury by reducing ferroptosis via the SLC7A11\/GPX4 pathway.<\/jats:p>","DOI":"10.1002\/adbi.202400180","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T23:54:33Z","timestamp":1727481273000},"source":"Crossref","is-referenced-by-count":10,"title":["Xinglou Chengqi Decoction Protects against Cerebral Ischemia\/Reperfusion Injury by Inhibiting Ferroptosis via SLC7A11\/GPX4 Signaling"],"prefix":"10.1002","volume":"8","author":[{"given":"Hua","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology Yixing Traditional Chinese Medicine Hospital  Yixing Jiangsu 214200 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyu","family":"Yue","sequence":"additional","affiliation":[{"name":"Division of Nephrology Jiangsu Province Hospital of Chinese Medicine Affiliated Hospital of Nanjing University of Chinese Medicine  Nanjing 210029 China"},{"name":"School of Integrated Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Yixing Traditional Chinese Medicine Hospital  Yixing Jiangsu 214200 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Yixing Traditional Chinese Medicine Hospital  Yixing Jiangsu 214200 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Yang","sequence":"additional","affiliation":[{"name":"Yixing Traditional Chinese Medicine Hospital  Yixing Jiangsu 214200 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu","family":"Lin","sequence":"additional","affiliation":[{"name":"Yixing Traditional Chinese Medicine Hospital  Yixing Jiangsu 214200 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5102-6916","authenticated-orcid":false,"given":"Jia","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology Yixing Traditional Chinese Medicine Hospital  Yixing Jiangsu 214200 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03051-2"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112445"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.1974810"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-00879-4"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002888"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2298-2"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.032"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154112"},{"key":"e_1_2_10_9_1","first-page":"1","volume":"2023","author":"Liu J.","year":"2023","journal-title":"Oxid. 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