Diterpenoids from the seeds of Euphorbia lathyris and their anti-inflammatory activity.

Twelve previously undescribed diterpenoids, euplarisans A-L (1-12), including one premyrsinane and eleven lathyranes, along with ten known analogues 13-22 were isolated from the seeds of Euphorbia lathyris. Their chemical structures were delineated by spectroscopic analysis and single-crystal X-ray diffraction. Interestingly, both 5 and 6 possessed an unusual trans-gem-dimethylcyclopropane as structural features and compound 8 was elucidated as premyrsinane-type diterpenoid. Meanwhile, a plausible biogenetic pathway for compounds 1-12 was proposed. In the anti-inflammatory bioassay, compounds 1, 2, 4, 13, 16, and 18 markedly inhibited the nitric oxide production in LPS-induced RAW264.7 macrophage cells. Compound 1 showed a more remarkable anti-inflammatory effect than others. It inhibited the generation of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and also obviously decreased the expression of iNOS, COX-2, and p-IκBα in a dose-dependent manner. The structure-activity relationships (SARs) of these diterpenoids were also discussed.