Ingenane diterpenoids with anti-inflammatory activity from the whole plants of Euphorbia peplus

Through phytochemical research on Euphorbia peplus, fourteen ingenane-type diterpenoids were identified. Among them, four previously undescribed compounds (1-4) were characterized, along with ten known analogues (5-14). Structural determination of the previously undescribed compounds was achieved by integrating data from HRESIMS, 1D, and 2D NMR spectroscopic analysis. A subset of the isolates, specifically compounds 1, 3, 4, 6, 11, 12, and 14, demonstrated significant reduction of NO production in LPS-stimulated RAW 264.7 macrophages, indicating anti-inflammatory potential. This investigation enhances the structural diversity among known ingenane diterpenoids and highlights their bioactivity relevant to inflammatory response modulation. Target screening and molecular docking suggest that the anti-inflammatory effect of compound 3 is likely mediated through its binding to human liver glycogen phosphorylase and protein kinase MK2.