Euphopias D-F from Euphorbia L.: quantum chemical calculation-based structure elucidation and their bioactivity of inhibiting NLRP3 inflammasome activation

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[10.2.1.0(2,10).0(5,9)]pentadecane core skeleton, compound 2 was the first example of an 8,9-norditerpenoid, possessing a tricyclic[8.3.0.0(2,8)]tridecane core skeleton, and compound 3 had a tricyclic[10.3.0.0(2,8)] 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-1 beta (IL-1 beta), thereby blocking GSDMD-mediated cell pyroptosis.

Automated summary

Three novel diterpenoids were isolated from Euphorbia helioscopia L., showing potential inhibitory effects on NLRP3 inflammasome. Among them, compound 1 exhibited the ability to inhibit the maturation of caspase-1 and regulate cytokine secretion, potentially blocking cell pyroptosis.