Euphopias D–F (1–3), three novel diterpenoids were isolated from Euphorbia helioscopia L. Comprehensive spectral analysis and a quantum chemical calculation strategy were employed to determine their structure. Compound 1 was defined by a unique caged tetracyclic[10.2.1.02,10.05,9]pentadecane core skeleton, compound 2 was the first example of an 8,9-norditerpenoid, possessing a tricyclic[8.3.0.02,8]tridecane core skeleton, and compound 3 had a tricyclic[10.3.0.02,8] pentadecane core skeleton. Biologically, compounds 1–3 exhibited a potential inhibitory effect on NLRP3 inflammasome. In particular, 1 could restrain the maturation of caspase-1 and regulate the secretion of cytokine interleukin-1β (IL-1β), thereby blocking GSDMD-mediated cell pyroptosis.
