Mechanism of Qidong Huoxue decoction in treatment of acute lung injury based on network pharmacology

AimTo explore the potential mechanisms of Qidong Huoxue decoction (QHD) in treating acute lung injury (ALI) using bioinformatics analysis and cell-based experiment.MethodsThe active components and predicted targets of QHD were retrieved from the TCMSP and HERB databases. ALI-related disease targets were obtained from the GeneCards and OMIM databases. The intersecting targets of the drug and disease were identified using Venny software, followed by the construction of a compound-target-disease network and a protein protein interaction (PPI) network. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to elucidate the biological functions and signaling pathways of the intersecting targets. Molecular docking was performed to evaluate the binding affinities between key compounds and target proteins. Furthermore, an in vitro lipopolysaccharide-induced macrophage inflammation model was established, and Western blot was used to validate the involvement of selected signaling proteins.ResultsA total of 20 active compounds and 488 ALI-related targets of QHD were identified. The top six key active compounds were emodin, quercetin, β-sitosterol, aloe-emodin, stigmasterol, and luteolin. The top ten hub targets included caveolin-1, EGFR, ESR1, MAPK3, JUN, PIK3CD, TLR4, S1P, SphK1, and TP53. GO enrichment analysis revealed 2, 534 biological processes (e. g., tyrosine peptide phosphorylation and modification), 109 cellular components (e. g., membrane lipid rafts and microdomains), and 191 molecular functions (e. g., serine/threonine kinase and tyrosine kinase activity). KEGG pathway analysis showed enrichment in lipid and atherosclerosis pathways and the PI3K/Akt signaling pathway. Molecular docking demonstrated that emodin had trong binding affinity (binding energy ≤-20.9 kJ·mol-1) with all core targets except TLR4. Western blot results confirmed that emodin significantly inhibited LPS-induced expression of inflammation-related proteins, including TLR4, caveolin-1, and phosphorylation of ERK/JNK in macrophages (P ConclusionsQidong Huoxue decoction exerts therapeutic effects against ALI by targeting multiple pathways, such as TLR4/NF-κB and MAPK signaling, and modulating lipid metabolism through its multi-component formulation (notably emodin).