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: (4 R ,5 R ,7 R )-7 β -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-3 α ,4 β -dihydroxy-1,6-dione ( 4 ), 19-norrosa-5,15-diene-3 α ,4 α -dihydroxy-1,6-dione ( 5 ), 19-norrosa-1,5,15-triene-3 α ,4 α -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 13 C-NMR. Among them, euphominoid Q ( 3 ) represents a rare 6/12-fused taxane-type diterpenoid, while 19-norrosa-5,15-diene-3 α ,4 β -dihydroxy-1,6-dione ( 4 ) and 19-norrosa-5,15-diene-3 α ,4 α -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 μ M 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.