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Recent studies have proved that LHQK exhibits excellent clinical efficacy in the treatment of acute lung injury (ALI). However, the corresponding mechanisms remain largely unexplored. In this study, we investigated the effects and the underlying mechanisms of LHQK on lipopolysaccharide (LPS)\u2010induced ALI in mice. The pathological examination, inflammatory cytokines assessments, and mucus secretion evaluation indicated that administration of LHQK ameliorated LPS\u2010induced lung injury, and suppressed the secretion of Muc5AC and pro\u2010inflammatory cytokines (IL\u20106, TNF\u2010\u03b1, and IL\u20101\u03b2) in plasma and BALF. Furthermore, the results of cell\u2010free DNA level showed that LHQK significantly inhibited LPS\u2010induced NETs formation. Western blot revealed that LHQK effectively inhibited LPS\u2010triggered pyroptosis in the lung. In addition, RNA\u2010Seq data analysis, relatively bioinformatic analysis, and network pharmacology analysis revealed that LHQK and relative components may play multiple protective functions in LPS\u2010induced ALI\/acute respiratory distress syndrome (ARDS) by regulating multiple targets directly or indirectly related to NETs and pyroptosis. In conclusion, LHQK can effectively attenuate lung injury and reduce lung inflammation by inhibiting LPS\u2010induced NETs formation and pyroptosis, which may be regulated directly or indirectly by active compounds of LHQK.<\/jats:p>","DOI":"10.1002\/pul2.12295","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T16:14:31Z","timestamp":1696608871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Lianhua Qingke ameliorates lipopolysaccharide\u2010induced lung injury by inhibiting neutrophil extracellular traps formation and pyroptosis"],"prefix":"10.1002","volume":"13","author":[{"given":"Wenjun","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Lung Inflammation and Injury  Shanghai 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