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This study investigates the protective effects of NACOS against acute lung injury (ALI) induced by lipopolysaccharides (LPS) in mice and explores its underlying metabolic regulatory mechanisms. Histopathological analysis showed that NACOS reduced pulmonary inflammation, edema, and disruption of tight junctions in ALI mice. Molecular analysis indicated that NACOS downregulated key inflammatory mediators, including NLRP3, IL-1\u03b2, TNF-\u03b1, MPO, and GCSF. Using untargeted metabolomics, glycerophospholipid metabolism was identified as the most significantly altered pathway following NACOS pre-treatment. Key regulated metabolites included triacylglycerols, phosphatidylethanolamines, lysophosphatidylcholines, and other glycerophospholipid derivatives. These findings suggest that NACOS exerts preventive effects through two primary mechanisms: the suppression of pro-inflammatory mediators and the modulation of glycerophospholipid metabolism. The identified metabolic alterations may serve as potential biomarkers for the progression of ALI and for monitoring prophylactic interventions.<\/jats:p>","DOI":"10.3390\/ijms26189128","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T14:45:46Z","timestamp":1758206746000},"page":"9128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["N-Acetylchitooligosaccharides Alleviate Pulmonary Inflammation and Modulate Glycerophospholipid Metabolism in Murine Acute Lung Injury"],"prefix":"10.3390","volume":"26","author":[{"given":"Xiongjie","family":"Sun","sequence":"first","affiliation":[{"name":"College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"},{"name":"School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengnan","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8006-4877","authenticated-orcid":false,"given":"Baifei","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"},{"name":"Hubei Shizhen Laboratory, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huabing","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junping","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0089-457X","authenticated-orcid":false,"given":"Haiming","family":"Hu","sequence":"additional","affiliation":[{"name":"Hubei Shizhen Laboratory, Wuhan 430061, China"},{"name":"Key Laboratory of Traditional Chinese Medicine Resource and Compound Prescription, Ministry of Education, Hubei University of Chinese Medicine, Wuhan 430065, China"},{"name":"School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0149-6389","authenticated-orcid":false,"given":"Hongtao","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"},{"name":"Hubei Shizhen Laboratory, Wuhan 430061, China"},{"name":"Key Laboratory of Traditional Chinese Medicine Resource and Compound Prescription, Ministry of Education, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Li, J., Deng, S.H., Li, J., Li, L., Zhang, F., Zou, Y., Wu, D.M., and Xu, Y. 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