In vitro and in silico evaluation of anti-inflammatory triterpene saponins from Elsholtzia penduliflora W.W. Smith (Lamiaceae).

Elsholtzia penduliflora W.W. Smith (Lamiaceae), a medicinal herb traditionally used in Vietnam, was investigated for its anti-inflammatory potential. Phytochemical analysis of its aerial parts, extracted using 80% ethanol, yielded 15 oleanane-type saponins (1-15) using chromatographic techniques. Among these, penduloside E (4), penduloside C (5), and kajiichigoside F1 (10) were prioritised for bioactivity testing based on structural characteristics and preliminary anti-inflammatory screening. These compounds at a concentration of 3 µM reduced PGE2 production by 48.9-54.3% and downregulated COX-2 mRNA expression by 36.6-42.4% in LPS-stimulated RAW 264.7 cells. Their effects were comparable to dexamethasone, which reduced PGE2 production by 59.8%, reaching 40.2% of the LPS control, and COX-2 mRNA to 33.3%. The compounds demonstrated low cytotoxicity, with cell viability consistently >80%. Molecular docking using AutoDock Vina revealed favourable binding interactions with COX-2 and iNOS enzymes, with compound 5 showing the highest binding affinities (-9.2 kcal/mol for COX-2; -8.7 kcal/mol for iNOS). Structural analysis revealed the triterpenoid backbone with feature functional groups may enhance bioactivity, suggesting structure-activity relationships. These findings suggest that E. penduliflora is a promising source of novel COX-2/iNOS inhibitors, with potential implications for the development of anti-inflammatory therapeutics.