Anti-inflammatory glycosides from Gomphandra mollis Merr.: Structural elucidation and mechanistic insights

Eight previously unreported glycosides, designated gomphandranosides I-VIII, along with nine known compounds, were isolated from the roots of Gomphandra mollis Merr. Their structures were elucidated through comprehensive spectroscopic analyses, including NMR, HR-ESI-MS, CD, DP4+ probability, and ECD calculations. The anti-inflammatory activities of the isolated compounds were assessed using nitric oxide inhibition assays in LPS-stimulated RAW264.7 macrophages. Compounds 5, 10, and 16 exhibited significant anti-inflammatory activity with IC₅₀ values of 7.56 ± 0.9, 15.0 ± 1.2, and 14.2 ± 0.9 μM, respectively. Network pharmacology, gene ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and molecular docking studies identified IL-6, TNF-α, MMP9, PTGS2, and HIF1A as key targets, with potentially involved in the NF-κB and IL-17 signaling pathways. These findings highlight G. mollis as a promising candidate for the treatment of inflammation-related diseases.