The dried roots of Euphorbia kansui (kansui) have been used for centuries in China as a herbal medicine for edema, ascites, and asthma. The 95% ethanol extract showed a significant inhibition of cell proliferation against human normal cell lines L-O2 and GES-1. Bioassay-guided separation of the 95% ethanol extract from the roots of E. kansui led to the isolation of 12 diverse terpenoids whose structures were identified by 1H, 13C NMR spectroscopy and ESI-MS as kansuinine A ( 1), kansuinine B ( 2), kansuinine C ( 3), kansuiphorin C ( 4), 3- O-(2' E,4' Z-decadienoyl)-20- O-acetylingenol ( 5), 3- O-(2' E,4' E-decadienoyl)-20- O-acetylingenol ( 6), 3- O-(2' E,4' Z-decadienoyl)-20-deoxyingenol ( 7), 3- O-benzoyl-20-deoxyingenol ( 8), 5- O-benzoyl-20-deoxyingenol ( 9), kansenone ( 1 0), epi-kansenone ( 11), euphol ( 12). All these 12 terpernoids were evaluated in vitro for cytotoxicity on L-O2 and GES-1 cell lines. Most ingenane-type diterpenoids and 8-ene-7-one triterpenoids ( 5– 11) exhibited a relatively lower IC 50 value; therefore, these compounds had stronger cytotoxicity against human normal cell lines L-O2 and GES-1 with dose-dependent relationships. These results will be signi？cantly helpful to reveal the mechanism of toxicity of kansui and to effectively guide safer clinical application of this herb.
References
[1]
Chinese Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China, 9th ed ed.; China Medical Science Press: Beijing, China, 2010; Volume I, p. 241.
[2]
Wu, T.S.; Lin, Y.M.; Haruna, W.; Pan, D.J.; Shingu, T. Kansuiphorbia A and B, two novel antileukemic deterpene ester from Euphorbia kansui. J. Nat. Prod 1991, 54, 823–829.
[3]
Miyata, S.; Wang, Y.L.; Yoshida, C. Inhibition of cellular proliferation by diterpenes, topoisomerase II inhibitor. Bioorg. Med. Chem 2006, 14, 2048–2051.
[4]
Wang, L.Y.; Wang, N.L.; Yao, X.S.; Miyata, S.; Kitanaka, S. Diterpenes from the roots of Euphorbia kansui and their in vitro effects on the cell division of Xenopus (2). Chem. Pharm. Bull 2003, 51, 935–941.
[5]
Wang, L.Y.; Wang, N.L.; Yao, X.S.; Miyata, S.; Kitanaka, S. Diterpenes from the roots of Euphorbia kansui and their in vitro effects on the cell division of Xenopus. J. Nat. Prod 2002, 65, 1246–1251.
[6]
Yu, F.R.; Lian, X.Z.; Guo, H.Y.; McGuire, P.M.; Li, R.D.; Wang, R.; Yu, F.H. Isolation and characterization of methyl esters and derivatives from Euphorbia kansui (Euphorbiaceae) and their inhibitory effects on the human SGC-7901 cells. J. Pharm. Pharmaceut. Sci 2005, 8, 528–535.
[7]
Li, X.R.; Zhang, Y.D.; Tang, H.H.; Wu, F.Y. Study of auxiliary therapeutic effect of kansui root on patients with severe acute pancreatitis (in Chinese). China J. Modern Med 2002, 12, 7–9.
[8]
Ouyang, J.B.; Deng, M.Y.; Ouyang, Y.M. Therapeutic effect on adjuvant treatment of severe acute pancreatitis with Euphorbia kansui Lious (in Chinese). China J. Modern Med 2004, 14, 96–97.
[9]
Lu, X.S.; Zhang, Y.; Ai, Y.H.; Li, Y.X. The clinical study of kansui root therapy for severe acute pancereatitis (in Chinese). J. Chin. Phys 2004, 6, 1444–1447.
[10]
Fan, Y.; Cai, D.F.; Gu, X.X.; Wang, G.H.; Ma, J. Treatment of intestinal obstruction with a large dose of kansui (in Chinese). J. Emerg. Tradit. Chin. Med 2005, 14, 278–279.
[11]
Liu, J.; Hong, L.J.; Guang, L.H.; Feng, W.L.; Bo, X.D.; Xian, M.F.; Ying, L.; Ning, Z. Treatment of postoperative intestinal obstruction in 504 cases with kansui (in Chinese). Chin. J. Critic. Care Med 1998, 18, 45.
[12]
Matsumoto, T.; Cyong, J.C.; Yamada, H. Stimulatory effects of ingenols from Euphorbia kansui on the expression of macrophage Fc receptor. Planta. Med 1992, 58, 255–258.
[13]
Zheng, W.F.; Cui, Z.; Zhu, Q. Cytotoxicity and antiviral activity of the compounds from Euphorbia kansui. Planta. Med 1998, 64, 754–756.
[14]
Huang, H.Y.; Shu, X.Y.; Ding, A.W.; Li, Z. Experimental study on purgative activity and acute toxicity of ethanol extracts from different polar parts of kansui and vinegar-preparing kansui (in Chinese). China Pharm. 2008, 17, 3–4.
[15]
Xiang, L.H.; Chen, Y.P.; Zhang, Z.; Shan, Z.Y.; Yu, Z.M.; Lv, A.P. The effect of 24 kinds toxic chinese medicine long-term toxicity experiments on rat organ index (in Chinese). Chin. J. Basic Med. Tradit. Chin. Med 2006, 12.
[16]
Yan, X.J.; Zhang, L.; Li, L.; Cao, Y.D.; Li, Z.J.; Tang, Y.P.; Ding, A.W. Study on detoxication of kansui radix on normal liver cells LO2 after stir-baking with vinegar (in Chinese). China J. Chin. Materia. Medica 2012, 37, 1667–1671.
[17]
Wang, L.Y. Study on chemical constituents and biological activity of kansui. Ph.D. Thesis, Shenyang Pharmaceutical University, Shenyang, China, July 2003.
[18]
Pan, Q.; Ip, F.C.; Ip, N.Y.; Zhu, H.X.; Min, Z.D. Activity of macrocyclic jatrophane diterpenes from Euphorbia kansui in a TrkA fibroblast survival assay. J. Nat. Prod 2004, 67, 1548–1551.
[19]
Pan, Q.; Min, Z.D. Studies on ingenol-type diterpene esters in root tuber of Euphorbia kansui (in Chinese). Chin. Tradit. Herb Drugs 2003, 34, 489–492.
[20]
Pan, D.J.; Qi, H.C.; Chang, J.J.; Lee, T.T.Y.; Chen, Y.P.; Hsu, H.Y.; McPhail, D.R.; McPhail, A.T.; Lee, K.H. Kansuiphorin C and D, cytotoxic diterpenes from Euphorbia kansui. Phytochemistry 1991, 30, 1018–1020.
[21]
Li, C.F. Studies of the constituents of the processed roots of Euphorbia kansui T.N.Wang. Master’s Thesis, Shenyang Pharmaceutical University, Shenyang, China, May 2006.
[22]
Uemura, D.; Ohwaki, H.; Hirata, Y. Isolation and structures of 20-deoxyingenol, new diterpene, derivatives, and ingenol derivative obtained from kansui. Tetrahedron Lett 1974, 29, 2527–2528.
[23]
Wang, Y.B.; Li, Y.Y.; Wang, H.B.; Qin, G.W. Chemical constituents from the roots of Euphorbia kansui. Chin. J. Nat. Med 2007, 5, 182–185.
[24]
Nunomura, S.; Kitanaka, S.; Ra, C. 3-O-(2,3-Dimethylbutanoyl)-13-O-decanoylingenol from Euphorbia kansui Suppresses IgE-Mediated Mast Cell Activation. Biol. Pharm. Bull 2006, 29, 286–290.
[25]
Zeng, Y.; Zhong, J.M.; Ye, S.Q.; Ni, Z.Y.; Miao, X.Q.; Mo, Y.K.; Li, Z.L. Screening of Epstein-Barr virus early antigen expression inducers from Chinese medicinal herbs and plants. Biomed. Environ. Sci 1994, 7, 50–55.
[26]
Shi, J.X.; Li, Z.X.; Nitoda, T.; Izumi, M.; Kanzaki, H.; Baba, N.; Kawazu, K.; Nakajima, S. Three antinematodal diterpenes from Euphorbia kansui. Biosci. Biotechnol. Biochem 2007, 71, 1086–1089.
[27]
Geng, T.; Huang, H.Y.; Ding, A.W.; Zhang, L. Irritation and diarrhea effect of different polar parts of Euphorbia kansui T. and vinegar preparing Euphorbia kansui T (in Chinese). Cent. South Pharm 2008, 6, 385–388.
[28]
Shu, X.Y.; Yu, L.; Tang, Y.P.; Zhang, L.; Ding, A.W.; Duan, J.A.; Shen, X.C. Bioassay-guided separation of the proinflammatory constituents from the roots of Euphorbia kansui. J. Nat. Med 2010, 64, 98–103.
[29]
Zhang, L.; Shu, X.Y.; Ding, A.W.; Yu, L.; Tang, Y.P.; Duan, J.A.; Shang, E.X.; Shen, X.C. LC-DAD-ESI-MS-MS Separation and chemical characterization of the inflammatory fraction of the roots of Euphorbia kansui. Chromatographia 2009, 70, 805–810.
[30]
Wang, Y.; Liu, J.; Cui, J.F.; Xing, L.X.; Wang, J.L.; Yan, X.; Zhang, X.H. ERK and p38 MAPK signaling pathways are involved in ochratoxin A-induced G2 phase arrest in human gastric epithelium cells. Toxicol. Lett 2012, 209, 186–192.
[31]
Yarim, M.; Koksal, M.; Durmaz, I.; Atalay, R. Cancer cell cytotoxicities of 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine derivatives. Int. J. Mol. Sci 2012, 13, 8071–8085.
