In vitro and in silico anti-inflammatory investigation of triterpenoids from combretum trifoliatum.

A saponin-enriched extract from the Combretum trifoliatum Vent. leaves (SE-CTL) exhibited notable in vitro anti-inflammatory activity, with an IC50 of 46.39 µg/mL against LPS-induced Nitric Oxide (NO) production in RAW264.7 macrophages. Phytochemical investigation of SE-CTL led to the isolation and structure elucidation of nine triterpenoids (1-9) using HRESIMS, NMR, and comparison with literature data. Notably, triterpene acids (1 and 5) were identified for the first time from the Combretum genus. Most compounds showed significant anti-inflammatory activity (IC50 = 25.55-36.87 µM), and triterpene acids (1-3) displayed moderate cytotoxicity against HT-29 and MKN-7 cells (IC50 = 69.94-98.06 µM). In silico studies suggested that their anti-inflammatory effects may involve inhibition of TLR4 and iNOS, with compound 1 showing strong TLR4 binding (ΔGMM-GBSA = -44.84 kcal/mol and stable RMSD during a 100-ns MD simulation). These findings highlight C. trifoliatum as a promising source of bioactive triterpenoids with anti-inflammatory potential.