Bio-Guided Isolation of the Cytotoxic Terpenoids from the Roots of Euphorbia kansui against Human Normal Cell Lines L-O2 and GES-1
Abstract
:1. Introduction
2. Results and Discussion
2.1. Identification of Compounds 1–12
2.2. Cytotoxicity Activity on Human Normal Cell Lines of Extracts and Compounds from Kansui
3. Experimental Section
3.1. Chemicals and Reagents
3.2. Instrumentation
3.3. Plant Material
3.4. Extraction and Isolation
3.5. Cell Line and Cell Culture
3.6. Cell Proliferation Analysis
3.7. Statistical Analysis
4. Conclusions
Acknowledgments
References
- Chinese Pharmacopoeia Commission, Pharmacopoeia of the People’s Republic of China, 9th ed; China Medical Science Press: Beijing, China, 2010; Volume I, p. 241.
- 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. [Google Scholar]
- Miyata, S.; Wang, Y.L.; Yoshida, C. Inhibition of cellular proliferation by diterpenes, topoisomerase II inhibitor. Bioorg. Med. Chem 2006, 14, 2048–2051. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- Zheng, W.F.; Cui, Z.; Zhu, Q. Cytotoxicity and antiviral activity of the compounds from Euphorbia kansui. Planta. Med 1998, 64, 754–756. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- Wang, L.Y. Study on chemical constituents and biological activity of kansui. Ph.D. Thesis, Shenyang Pharmaceutical University, Shenyang, China, July 2003. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar]
Position | 1 | Position | 2 | 3 |
---|---|---|---|---|
1 | 2.66 (dd, 6.3, 14.1) | 1 | 4.33 (brs) | 4.94 (s) |
2.25 (m) | ||||
2 | 2.10 (m) | 2 | - | - |
3 | 5.60 (brs) | 3 | 5.53 (d, 4.8) | 5.38 (d, 4.7) |
4 | 2.98 (brs) | 4 | 3.63 (dd, 11.4, 5.0) | 3.48 (m) |
5 | 6.15 (s) | 5 | 5.93 (d, 5.85) | 5.95 (s) |
7 | 6.44 (s) | 7 | 5.88 (s) | 5.88(s) |
8 | 6.05 (s) | 8 | 4.66 (brs) | 4.70 (d, 9.3) |
9 | 5.09 (s) | 9 | - | - |
11 | 4.14 (s) | 11 | 3.70 (d, 1.8) | 3.65 (d, 2.04) |
12 | - | 12 | 3.33 (m) | 3.46 (m) |
13 | 2.33 (q, 6.6) | 13 | 3.38 (m) | 3.26 (m) |
16 | 0.936 (d, 6.6) | 16 | 1.29 (s) | 1.32 (s) |
17 | 5.24 (s) | 17 | 6.52 (s) | 6.390 (s) |
5.14 (s) | 5.94 (s) | 5.95 (s) | ||
18 | 1.31 (s) | 18 | 1.35 (s) | 1.33 (s) |
19 | 1.15 (s) | 19 | 0.85 (s) | 0.89 (s) |
20 | 1.32 (d, 6.3) | 20 | 1.53 (d, 6.27) | 1.65 (d, 6.51) |
Acetyls | - | Acetyls | - | - |
COMe-1 | - | COMe-1 | - | 2.14 (s) |
COMe-3 | 2.10 (s) | COMe-3 | 1.90 (s) | 1.95 (s) |
COMe-5 | 2.08 (s) | COMe-5 | - | - |
COMe-7 | 2.19 (s) | COMe-7 | - | - |
COMe-9 | 2.01 (s) | COMe-9 | - | - |
COMe-15 | 1.96 (s) | COMe-15 | 2.32 (s) | - |
Benzoyls | - | Benzoyls | - | - |
COPh-8 -2,6 | 8.05 (m) | COPh-5-2,6 | 7.56 (m) | 7.48 (m) |
-3,5 | 7.44 (m) | -3,5 | 7.03 (m) | 6.88 (m) |
-4 | 7.55 (m) | -4 | 7.22 (m) | 7.06 (m) |
COPh-7-2,6 | - | COPh-7-2,6 | 7.51 (m) | 7.53 (m) |
-3,5 | - | -3,5 | 6.93 (m) | 7.02 (m) |
-4 | - | -4 | 7.10 (m) | 7.25 (m) |
OH-1 | - | OH-1 | 3.94 (brs) | - |
OH-2 | - | OH-2 | 2.53 (m) | 2.33 (s) |
OH-8 | - | OH-8 | 3.59 (m) | 3.50 (m) |
OH-15 | - | OH-15 | - | 4.10 (s) |
Position | 4 | 5 | 6 | 7 | 8 | 9 |
---|---|---|---|---|---|---|
1 | 6.14 (brs) | 6.05 (s) | 6.04 (s) | 6.07 (s) | 6.14 (s) | 6.02 (s) |
3 | 5.07 (s) | 5.60 (s) | 5.57 (s) | 5.53 (s) | 5.67 (s) | 3.73 (s) |
5 | 5.51 (brs) | 3.88 (s) | 3.88 (s) | 3.68 (s) | 3.76 (brs) | 5.41 (s) |
7 | 5.88 (d, 1.5) | 6.12 (d, 3.7) | 6.12 (d, 3.7) | 5.76 (m) | 5.78 (m) | 5.91 (m) |
8 | 4.26 (dd, 9.5, 1.5) | 4.08 (dd, 4.0, 11.7) | 4.08 (dd, 4.0, 11.7) | 4.02 (dd, 9.9, 3.0) | 4.03 (m) | 4.13 (dd, 7.0, 14.2) |
11 | 2.31 (m) | 2.49 (m) | 2.48 (m) | 2.46 (m) | 2.54 (m) | 2.41 (m) |
12 | 2.54 (m) | 2.26 (m) | 2.26 (m) | 2.26 (m) | 2.28 (m) | 2.34 (m) 1.77 |
1.73 (m) | 1.75 (m) | 1.76 (m) | 1.74 (m) | 1.75 (m) | (m) | |
13 | 0.74 (m) | 0.72 (m) | 0.72 (m) | 0.67 (m) | 0.67 (m) | 0.70 (m) |
14 | 0.88 (m) | 0.98 (m) | 0.98 (m) | 0.90 (m) | 0.93 (m) | 0.94 (m) |
16 | 1.07 (s) | 1.06 (s) | 1.06 (s) | 1.05 (s) | 1.04 (s) | 1.07 (s) |
17 | 1.13 (s) | 1.08 (s) | 1.08 (s) | 1.08 (s) | 1.06 (s) | 1.17 (s) |
18 | 1.00 (d, 4.7) | 1.00 (d, 7.3) | 1.00 (d, 7.3) | 0.99 (d, 7.2) | 1.05 (d, 4.2) | 0.98 (d, 5.61) |
19 | 1.78 (brs) | 1.8 (d, 1.1) | 1.8 d (1.1) | 1.80 (brs) | 1.83 (d, 1.5) | 1.83 (s) |
20 | 1.56 (s) | 4.75, 4.49 (Abq, 12.5) | 4.75, 4.49 (Abq, 12.5) | 1.79 (s) | 1.81 (s) | 1.60 (s) |
3-R, 2′ | 8.13 (m) | 5.95 (d, 15.3) | 5.86 (d, 15.3) | 5.95 (d, 5.1) | 8.04 (d, 7.3) | - |
3′ | 7.48 (m) | 7.70 (m) | 7.31 (m) | 7.68 (dd, 15.3, 11.4) | 7.48 (t, 7.6) | - |
4′ | 7.60 (m) | 6.16 (m) | 6.21 (m) | 6.16 (m) | 7.61 (t, 7.3) | - |
5′ | - | 5.95 (m) | 6.21 (m) | 5.94 (m) | - | - |
6′ | - | 2.29 (m) | 2.20 (m) | 2.34 (m) | - | - |
7′ | - | 1.43 (m) | 1.43 (m) | 1.43 (m) | - | - |
8′ | - | 1.31 (m) | 1.31 (m) | 1.29 (m) | - | - |
9′ | - | 1.28 (m) | 1.28 (m) | - | - | |
10′ | - | 0.89 (t, 7.0) | 0.72 (t, 7.0) | 0.89 (m) | - | - |
OAc | - | 2.06 (s) | 2.05 (s) | - | - | - |
5-R, 2′ | 2.05 (s) | - | - | - | - | 8.10 (m) |
3′ | - | - | - | - | - | 7.46 (m) |
4′ | - | - | - | - | - | 7.60 (m) |
Position | 10 | 11 |
---|---|---|
1α | 1.44 (m) | 1.44 (m) |
1β | 1.86 (m) | 1.86 (m) |
2 | 1.76 (m) | 1.75 (m) |
1.67 (m) | 1.66 (m) | |
3α | 3.29 (dd, 4.6,11.6) | 3.29 (dd, 4.6,11.6) |
5α | 1.67 (m) | 1.66 (m) |
6α | 2.40 (m) | 2.41 (m) |
6β | 2.38 (m) | 2.38 (m) |
11α | 2.37 (m) | 2.36 (m) |
11β | 2.24 (m) | 2.24 (m) |
12α | 1.76–1.80 (m) | 1.76–1.80 (m) |
15α | 1.55 (m) | 1.55 (m) |
15β | 2.12 (m) | 2.12 (m) |
16α | 1.34 (m) | 1.34 (m) |
16β | 1.93 (m) | 1.94 (m) |
17 | 1.44 (m) | 1.46 (m) |
18 | 0.73 (s) | 0.73 (s) |
19 | 1.06 (s) | 1.05 (s) |
20 | 1.41 (m) | 1.43 (m) |
21 | 0.88 (d, 6.0) | 0.93 (d, 6.1) |
22 | 1.13 (m), 1.55 (m) | 1.05 (m), 1.48 (m) |
23 | 1.90 (m), 2.04 (m) | 1.82 (m), 2.04 (m) |
24 | 5.09 (m) | 5.10 (m) |
26 | 1.69 (s) | 1.68 (s) |
27 | 1.61 (s) | 1.60 (s) |
28 | 0.99 (s) | 0.99 (s) |
29 | 0.88 (s) | 0.88 (s) |
30 | 0.97 (s) | 0.96 (s) |
Extract/Compounds | IC50 | |
---|---|---|
L-O2 | GES-1 | |
EtOH extract | 42.02 μg/mL | 30.67 μg/mL |
EtOAc extract | 27.08 μg/mL | 21.89 μg/mL |
Water extract | >100 μg/mL | >100 μg/mL |
1 | >100 μM | >100 μM |
2 | >100 μM | >100 μM |
3 | >100 μM | >100 μM |
4 | >100 μM | >100 μM |
5 | 12.40 μM | 8.51 μM |
6 | 8.22 μM | 6.67 μM |
7 | 13.08 μM | 3.53 μM |
8 | 70.78 μM | 23.51 μM |
9 | 34.53 μM | 22.01 μM |
10 | 14.36 μM | 13.44 μM |
11 | 17.82 μM | 8.04 μM |
12 | >100 μM | >100 μM |
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
Share and Cite
Zhang, L.; Gao, L.; Li, Z.; Yan, X.; Yang, Y.; Tang, Y.; Cao, Y.; Ding, A. Bio-Guided Isolation of the Cytotoxic Terpenoids from the Roots of Euphorbia kansui against Human Normal Cell Lines L-O2 and GES-1. Int. J. Mol. Sci. 2012, 13, 11247-11259. https://doi.org/10.3390/ijms130911247
Zhang L, Gao L, Li Z, Yan X, Yang Y, Tang Y, Cao Y, Ding A. Bio-Guided Isolation of the Cytotoxic Terpenoids from the Roots of Euphorbia kansui against Human Normal Cell Lines L-O2 and GES-1. International Journal of Molecular Sciences. 2012; 13(9):11247-11259. https://doi.org/10.3390/ijms130911247
Chicago/Turabian StyleZhang, Li, Lan Gao, Zhengjun Li, Xiaojing Yan, Yanjing Yang, Yuping Tang, Yudan Cao, and Anwei Ding. 2012. "Bio-Guided Isolation of the Cytotoxic Terpenoids from the Roots of Euphorbia kansui against Human Normal Cell Lines L-O2 and GES-1" International Journal of Molecular Sciences 13, no. 9: 11247-11259. https://doi.org/10.3390/ijms130911247
APA StyleZhang, L., Gao, L., Li, Z., Yan, X., Yang, Y., Tang, Y., Cao, Y., & Ding, A. (2012). Bio-Guided Isolation of the Cytotoxic Terpenoids from the Roots of Euphorbia kansui against Human Normal Cell Lines L-O2 and GES-1. International Journal of Molecular Sciences, 13(9), 11247-11259. https://doi.org/10.3390/ijms130911247