Qingjin Huatan decoction attenuates lipopolysaccharide-induced acute lung injury in mice by controlling platelet-associated formation of neutrophil extracellular traps

Abstract Background Acute lung injury (ALI) is a severe and life-threatening lung inflammation with high morbidity and mortality, underscoring the importance to develop effective drugs. Qingjin Huatan decoction (QJHTD), as a classic ancient prescription, has been widely used for treating respiratory diseases. However, the role and mechanism of QJHTD against ALI remain unclear. Objective This study aimed to explore the therapeutic effect of QJHTD on lipopolysaccharide (LPS)-induced ALI in mice and uncover its mechanism. Methods The therapeutic effect of QJHTD on LPS-induced ALI in mice was evaluated by the histopathological changes in the lung tissue, the lung wet/dry weight ratio, and the levels of inflammatory cytokines and thrombin-antithrombin complexes. Transcriptomics was used to predict the mechanism of QJHTD in treating ALI. The expression levels of citrullinated histone 3 in the lung tissue, the content of cell-free DNA in the bronchoalveolar lavage fluid (BALF), and the platelet-associated formation of neutrophil extracellular traps (NETs) in vitro were determined. Results Qingjin Huatan decoction exerted protective effect against LPS-induced ALI by suppressing interstitial edema, maintaining the alveolar-capillary barrier, inhibiting the infiltration of neutrophils and platelets in the lung tissue, and lowering the levels of tumor necrosis factor α, interleukin 1β, interleukin 6, and thrombin-antithrombin complexes in BALF. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the formation of NETs was the main regulatory pathway for QJHTD against ALI. Qingjin Huatan decoction could treat ALI by inhibiting the release of NETs via reducing the content of citrullinated histone 3 in lung tissue and cell-free DNA in BALF in vivo, and suppressing the NETs formation induced by LPS-stimulated platelets under flow and static conditions in vitro. The formation of NETs was considered to bridge the interactions between neutrophils and platelets. Conclusions This research demonstrated the effects of QJHTD in treating ALI and provided new insights for clarifying the complex regulation of neutrophils, platelets, and NETs in ALI.