Terpenoids in Euphorbia milii Ch. des Moulins and their anti-rheumatic potential

Seven previously undescribed terpenoids (1-7) and sixteen known terpenoids (8-23) were isolated from Euphorbia milii Ch. des Moulins. Among the undescribed terpenoids, there is one eremophilane-type sesquiterpenoid: (4R,5R,7R)-7β-hydroxy-eremophil-1(10),11-diene-2-one (1); one abietane-type diterpenoid: 9-hydroxycaudicifolin (2); one taxane-type diterpenoid: euphominoid Q (3); three norrosane-type diterpenoids: 19-norrosa-5,15-diene-3α,4β-dihydroxy-1,6-dione (4), 19-norrosa-5,15-diene-3α,4α-dihydroxy-1,6-dione (5), 19-norrosa-1,5,15-triene-3α,4α-diol (6); and one taraxerane triterpenoid: aleuritolic acid-3-cis-p-hydroxycinnamate (7). The structures of these compounds were elucidated including nuclear magnetic resonance (NMR), mass spectrometry, X-ray single-crystal diffraction, and calculated ¹³C-NMR. Among them, euphominoid Q (3) represents a rare 6/12-fused taxane-type diterpenoid, while 19-norrosa-5,15-diene-3α,4β-dihydroxy-1,6-dione (4) and 19-norrosa-5,15-diene-3α,4α-dihydroxy-1,6-dione (5) are epimers. In vitro bioactivity assays revealed that 9-hydroxycaudicifolin (2) and caudicifolin (20), two abietane-type diterpenoids with anti-rheumatic potential, exhibited stronger inhibitory effects on the production of the inflammatory cytokine NO at 50 μM than the positive control celecoxib. Furthermore, both compounds inhibited the proliferation of MH7A cells, which are synovial fibroblasts derived from rheumatoid arthritis patients. Preliminary observations indicated that compound 2 could induce apoptosis in MH7A cells, arrest the cell cycle of MH7A cells at the G2 phase in a concentration-dependent manner.