First discovery of triterpenoids and sterols from Cotinus coggygria var. cinereus Engl. with anti-inflammatory and antibacterial activities.

This study led to the isolation of 17 triterpenoids, including two lanostane-type (1 and 2), two dammarane-type (3 and 7), ten tirucallane-type (4 and 8-16), and three oleanane-type (17-19) triterpenoids, as well as nine sterols (5, 6, and 20-26) from Cotinus coggygria var. cinereus Engl, which were first discovered from the genus Cotinus. Among them, coggygrenoids A-D (1-4), coggygrerol A (5), and coggygrerol B (6) are undescribed compounds. Additionally, seven flavonoids (27-33) were also isolated from this plant. Compound 15 displayed inhibitory activities in LPS-induced RAW 264.7 cells with an IC50 value 6.81 ± 0.15 μM. Molecular docking demonstrated that 15 exhibited favorable affinity for NLRP3 and iNOS. In vitro and in vivo antibacterial evaluations indicated that coggygrnoid C (3) exhibited significant inhibitory activity against methicillin-resistant Staphylococcus aureus ATCC BAA-1717 (USA300), with An MIC of 8 μg/mL. Further mechanistic investigations demonstrated that 3 exerted antibacterial activity by compromising the integrity of the cell wall and membrane. Notably, the combination of 3 with ampicillin exhibited an additive antibacterial effect. In the Galleria mellonella infection model, compound 3 exhibited comparable activity to that of the positive control at 20 mg/kg. These findings suggest that triterpenoids of C. coggygria are potential antibacterial lead agents.