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Warifteine, which is a traditional remedy known for its antiinflammatory properties, has been identified, but its potential effects on ALI remain unexplored. In this study, a murine model of ALI was established by injecting LPS into wild-type (WT) or neutrophil-specific Gsdmd (Gasdermin D)\u2013deficient mice. Pulmonary function was evaluated, and lung samples were collected for immunofluorescence staining and RNA sequencing analysis. Additionally, live imaging of the lungs as well as histological, biochemical, and molecular investigations were performed to assess the progression of LPS-induced ALI in mice. Mouse bone marrow\u2013derived neutrophils were isolated and cultured to investigate the effects of warifteine in vitro. Our findings indicate that warifteine effectively mitigates LPS-induced lung pathology and dysfunction in mice. Mechanistic studies revealed that warifteine protects against ALI by inhibiting neutrophil extracellular trap formation and the resulting cytokine storm. Subsequent research demonstrated that warifteine influences neutrophil extracellular trap formation by inhibiting GSDMD oligomerization through the regulation of reactive oxygen species production by neutrophils. Collectively, these findings reveal a novel role for warifteine in the protection against ALI and suggest that modulating GSDMD oligomerization may be an innovative therapeutic strategy.<\/jats:p>","DOI":"10.1165\/rcmb.2024-0472oc","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T09:33:35Z","timestamp":1741685615000},"page":"559-571","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":5,"title":["Warifteine Alleviates Acute Lung Injury and Inhibits NETosis by Decreasing Reactive Oxygen Species\u2013induced Gasdermin D Oligomerization"],"prefix":"10.1093","volume":"73","author":[{"given":"Qian","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhukai","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Urology, Shanghai Changhai Hospital, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Automation & Institute for Brain and Cognitive Sciences, Tsinghua University, Beijing 100084, China"},{"name":"Zhejiang Hehu Technology, Hangzhou 311121, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"Shao","sequence":"additional","affiliation":[{"name":"Postdoctoral Station of Basic Medicine, Xiangya Hospital, Central South University, Changsha 410000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xie","sequence":"additional","affiliation":[{"name":"Postdoctoral Station of Basic Medicine, The Second Xiangya Hospital, Central South University, Changsha 410000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"2026012204142722800_bib1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41572-019-0069-0","article-title":"Acute respiratory distress syndrome","volume":"5","author":"Matthay","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"2026012204142722800_bib2","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1164\/rccm.201609-1773CP","article-title":"Fifty years of research in ARDS. 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