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.