Three New Clerodane Diterpenoids and Their NLRP3 Inflammasome Activation Inhibitory Activity from Callicarpa arborea Roxb

Abstract

AbstractThree new compounds callicarpenoids A−C (1–3), were isolated from the stems of Callicarpa arborea Roxb together with fifteen known compounds (4–18). The structures of these compounds were elucidated using advanced spectroscopic techniques, including 1D and 2D NMR, UV, IR, HR‐ESI‐MS, ECD, ORD, and quantum chemical calculations. Compound 3, a rare rearranged diterpenoid with a fused 5/6‐ring system demonstrated strong potential as an inhibitor of the NLRP3 inflammasome activation with an IC50 value of 3.153 μM. It effectively reduced GSDMD‐NT production, inhibited caspase‐1 activation, and suppressed IL‐1β secretion, thereby mitigating NLRP3 inflammasome‐induced pyroptosis in J774A.1 cells. These findings suggest that compound 3 warrants further research and development as a promising NLRP3 inflammasome inhibitor.