Mechanism Investigation of Sophora davidii Flower Extract Against LPS-Induced Acute Lung Injury Based on Network Pharmacology and Molecular Dynamics Simulation

Aim: Acute lung injury (ALI) is a common respiratory disease that significantly contributes to morbidity and mortality. Sophora davidii flower extract (SDFE), used both as a vegetable and a traditional medicine, has shown potential to alleviate ALI, but the associated underlying mechanisms remain unknown. This study aimed to elucidate the mechanisms through which SDFE protects against ALI. Methods: Key signaling pathways, molecular targets, and bioactive compounds associated with the anti-ALI effects of SDFE were predicted using network pharmacology. Lipopolysaccharide (LPS)-induced ALI models were established in BEAS-2B cells and rats. The protective effects of SDFE were investigated by measuring the tissue injury markers alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in lung tissue and bronchoalveolar lavage fluid (BALF). Representative proteins in the main pathways were validated using molecular docking, molecular dynamics simulation, and experimental assays. Results: Network pharmacology analysis identified 363 SDFE targets closely associated with ALI, including the endothelial injury markers intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). The results of molecular docking and molecular dynamics simulations demonstrated that ICAM-1 and VCAM-1 have strong binding affinity for quercetin and matrine. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that leukocyte adhesion and oxidative stress are two key signaling pathways involved in the therapeutic effects of SDFE against ALI. SDFE significantly reduced ALP, LDH, and nitric oxide (NO) levels in lung tissue and BALF from ALI rats and markedly inhibited neutrophil elastase (NE) and myeloperoxidase (MPO) expression in lung tissue. In LPS-stimulated BEAS-2B cells, SDFE downregulated the mRNA expression of ICAM-1 and VCAM-1, the protein expression of MPO, and the level of NO. Conclusions: SDFE can ameliorate LPS-induced ALI by inhibiting leukocyte adhesion and reducing oxidative stress.