Exploring the immunomodulatory potential of Lilium lancifolium in pneumonia: a combined study of network pharmacology, molecular docking, and in vitro experiments.

Pneumonia remains a major global health challenge characterized by excessive inflammation and immune imbalance. Lilium lancifolium, a traditional medicinal plant with anti-inflammatory and immunomodulatory properties, may have therapeutic potential. This study aimed to explore its potential targets and pathways in pneumonia. Active compounds of Lilium lancifolium were screened via TCMSP and SwissTargetPrediction, and intersected with pneumonia-related genes retrieved from the GeneCards database. Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, protein-protein interaction (PPI) analysis, and molecular docking were implemented to probe putative targets. A549 and THP-1-derived macrophages were used for in vitro validation. Cell viability (CCK-8), cytokine levels (ELISA), protein expression (Western blot), gene expression (qRT-PCR), and immunofluorescence were assessed. Network pharmacology identified four potential key targets (SRC, ALOX5, PLG, SYK) associated with representative flavonoids, including quercetin, kaempferol, and hesperetin. Enrichment analysis indicated involvement in immune and inflammatory pathways. Molecular docking suggested favorable binding, especially between quercetin and SYK (binding energy < - 7.5 kcal/mol). In vitro, LLE significantly alleviated LPS-induced injury in A549 and THP-1 cells, reduced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and increased IL-10 (P < 0.001), and suppressed SYK/NF-κB activation and M1-associated macrophage polarization (P < 0.001), indicating its potential anti-inflammatory effects. Lilium lancifolium may exert anti-inflammatory effects through multi-target and multi-pathway regulation, potentially involving the SYK/NF-κB signaling axis and macrophage polarization. This study provides preliminary evidence supporting its potential application in inflammatory lung diseases.