The Chemical Composition And Biological Activity Of Euphorbia

Euphorbia kansui L. (Euphorbiaceae) is abundantly distributed in the northwesten China. The dried roots of Euphorbia kansui are known as "Kan Sui" in Chinese medicine. "Kan Sui" was recorded in Sheng Nung 's Herbal as a low grade drug and has been used as a herbal remedy for edema, ascites, and cancer. Previous investigations of E. kansui have yielded numerous ingenane-type diterpenes and euphane/tirucallane-type triterpenes.In our investigations of biologically active and/or structurally novel substances from Kan Sui, 41 compounds were isolated with silica gel, ODS C-18, and HPLC, etc. Among them, 38 compounds were elucidated on the basis of chemical and spectral methods. The eighteen new compounds were named as 20-O-(2'E,4'E-decadienoyl)ingenol (1), 20-O-(2'E,4'Z-decadienoyl)ingenol (2), 3-O-(2'E,4'E-decadienoyl)ingenol (4), 3-O-(2'E,4'Z-decadienoyl)-5-O-acetylingenol (5), 3-O-(2'E,4'E-decadienoyl)-20-O-acetylingenol (7), 5-O-(2'E,4'E-decadienoyl)ingenol (9), 3-0-(2'E,4'Z-decadienoyl)-2O-deoxyingenol (10), 3-O-(2'E,4'E-decadienoyl)-20-deoxyingenol (11), 3-O-(2,3-dimethylbutanoyl)-l 3-O-dodecanoyl-20-O-acetyIingenol (15), 3-O-(2,3-dimethylbutanoyl)-13-O-dodecanoyl-20-deoxyingenol (16), Kansuinins C, D, E (22, 24, 26), Kansenonol (27), Kansenone (28), Epi-kansenone (29), 11-Oxo-kansenonol (30), Kansenol (31) Together with 20 known compounds: 3-O-(2E,4'Z-decadienoyl)ingenol (3), 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (6), 20-O-decanoylingenol (8), kansuiphorin D (12), 5-O-benzoyl-2O-deoxyingenol (13), 3-0-benzoyl-2O-deoxyingenol (14), 3-O-(2,3-dimethylbutanoyl)-13-O-dodecanoylingenol (17), 3-O-(2,3-dimethylbutanoyl)-13-0-decanoylmgenol (18), 20-O-(2,3-dimethylbutanoyl)-l3-O-dodecanoylingenol (19), 3-O-benzoyl-13-O-dodecanoylingenol (20), 20-O-benzoyl-13-O-dodecanoylingenol (21), kansuinin B (23), kansuinin A (25), euphol (32), tirucallol (33), P-sitosterol (34), Stigmast-5-ene-3p,7P-diol (35), Stigmaist-5-ene-3p,7a-diol (36), isoscopletin (37), palmitic acid (38) Among them, compounds 8, 20, 21, 35, and 36 were isolated fromthis genus for the first time; compounds 18 and 19 were isolated from this plant for the first time.We tested the cell cleavage arrest activity of 17 compounds using an animal cap assay. The studies on the structure-activity relationship of these compounds were also investigated. We found that ingenane-type diterpenes induced the greatest cell cleavage arrest, but cell cleavage inhibitory activity became weak when C-13 had an acyl residue. In contrast, in jatrophane diterpenes, only kansuinin B (23) showed some activity. In euphane/tirucallane triterpenes, those compounds with 8-ene-7-one residue showed some activity.16 compounds were tested their effects on NO production inhibitory activity using macroiphage RAW 264.7 cells. Ingenane-type diterpenes showed significant NO production inhibitory activity, but these compounds also showed cytotoxity. When C-3 or C-13 had an acyl residue, cytotoxity became weak. In euphane/tirucallane triterpenes, those compounds with 8-ene-7-one residue showed strong activity. Jatrophane compounds (23,25) showed no NO inhibitory activity.