Abstract
Polygonatum odoratum is widely consumed as a functional food and is traditionally used for respiratory complaints, yet the material basis of its anti-pneumonia activity and the effect of extraction solvent on that activity remain unclear. Here, untargeted LC-QTOF-MS profiling of the aqueous extract was combined with TCMSP database mining to screen potential active components, and their core targets and binding modes were predicted by network pharmacology and molecular docking. Of 38 potential active components screened by oral bioavailability and drug-likeness, 28 were mapped to 123 pneumonia-related targets. IL6, AKT1, IL1B, TNF, TGFB1, TP53, MMP9, PIK3CG, HIF1A and CASP3 occupied hub positions in the PPI network and were enriched in the IL-17, TNF and PI3K-Akt pathways. Molecular docking of 7 representative components against 9 core targets gave 24 systems with binding energies all below −4.8 kcal/mol, and different components frequently occupied the same binding pocket, indicating a multi-component, multi-target mode of action. Critically, all nine docking targets were functionally interrogated in LPS/IFN-γ-stimulated MLE-12 cells: the 50% methanol extract significantly improved 9 of 10 indicators, outperforming the aqueous extract on all 10, with significant differences in p-AKT and p-CREB (P < 0.05). Medium-lipophilic homoisoflavonoids are therefore the principal material basis of the anti-pneumonia activity, and hydroalcoholic extraction better retains them. These findings support the use of P. odoratum as a functional food ingredient for respiratory health.