乌头属药物资源的化学和生物学研究进展

doi:10.5246/jcps.2013.03.030

摘要/Abstract

摘要：

毛茛科乌头属药用植物含有二萜生物碱、多糖、黄酮类等药物活性成份, 促进了对其化学分类学、分子分类学和药理学的研究。作为药用植物亲缘学的继续深入研究, 本文综述乌头属的植物化学、化学分类、分子生物学和系统发育等方面的近期进展及其与乌头药效和毒性的关联。近年在多种乌头植物中发现了更多二萜生物碱, 以 C19: III, aconitine 类型最多。综述了近年发现的乌头生物碱和提取物, 以及乌头多糖和其它成分的生物活性。国产乌头亚属中乌头组基于形态学的11系分类未得到化学分类和分子系统发育研究的支持。基于细胞核和叶绿体DNA序列的分子系统树将形态极相近的9系分为两群, 一为甘青乌头系, 圆叶乌头系, 保山乌头系和短柄乌头系; 另一为乌头系, 兴安乌头系, 显柱乌头系, 蔓乌头系和准噶尔乌头系, 化学分类数据支持此分群。为了乌头资源的可持续利用和发现高效低毒的新化合物, 有必要将近年涌现的新技术用于乌头研究。系统生物学和组学技术将在促进乌头生物活性化合物研究中发挥关键作用。

关键词: 乌头属, 植物化学, 生物活性, 化学分类学, 系统发育, 药物资源

Abstract:

Many herbal medicines have so far been utilized for the treatment of various ailments since the beginning of Chinese civilization. Aconitum is a botanical source for various pharmaceutically active components, which has been commonly used in traditional Chinese medicine for thousands of years. Increasing interest in Aconitum pharmaceutical resources has led to further discoveries of diterpenoid alkaloids, polysaccharides, flavonoids and many other compounds in various Aconitum species, and to investigations on their chemotaxonomy, molecular phylogeny and pharmacology. In continuation with our studies on Aconitum pharmacophylogeny, here we review the phytochemistry, chemotaxonomy, molecular biology and phylogeny of Aconitum and their relevance to therapeutic efficacy and toxicity. An exhaustive literature survey is used to summarize the global scientific effort in the phytochemical and biological studies of Aconitum. More diterpenoid alkaloids have been found in various Aconitum species, among which the aconitine type (type III) is predominant. The versatile bioactivities of alkaloids and extracts, as well as the bioactivities of polysaccharides and other ingredients, are summarized and discussed in this review. The morphology-based 11-series classification of section Aconitum, subgenus Aconitum, is not supported by chemotaxonomy and molecular phylogeny. Molecular phylogeny based on nuclear and chloroplast DNA sequences divided the nine morphologically similar series into two clusters, which is bolstered by the chemotaxonomic data. It is essential to integrate the emerging technologies into Aconitum studies for both the sustainable utilization of Aconitum pharmaceutical resources and finding novel compounds with potential clinical utility and less toxicity. Systems biology and omics technologies will play an increasingly important role in booming pharmaceutical research involving bioactive compounds of Aconitum.

Key words: Aconitum, Phytochemistry, Biological activity, Chemotaxonomy, Phylogeny, Pharmaceutical resource

中图分类号:

R284

Supporting: Foundation item: Dalian Jiaotong University and Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Science and Technology National Support Program (Grant No. 2012BAI29B01).
^*Corresponding author. Tel.: 86-411-84572552

郝大程^*, 顾晓洁, 肖培根^*, 许利嘉, 彭勇. 乌头属药物资源的化学和生物学研究进展[J]. , DOI: 10.5246/jcps.2013.03.030.

Dacheng Hao^*, Xiaojie Gu, Peigen Xiao^*, Lijia Xu, Yong Peng . Recent advances in the chemical and biological studies of Aconitum pharmaceutical resources [J]. , DOI: 10.5246/jcps.2013.03.030.

参考文献

[1] Xiao, P.G.; Wang, F.P.; Gao, F.; Yan, L.P.; Chen, D.L.; Liu, Y. Acta Phytotaxo. Sin. 2006, 44, 1-46.
[2] Jabbour, F.; Renner, S.S. Mol. Phylogenet. Evol. 2012, 62, 928-942.
[3] Luo, Y.; Zhang, F.M.; Yang, Q.E. Plant Syst. Evol. 2005, 252, 11-25.
[4] Luo, Y.; Yang, Q.E. Acta Phytotaxo. Sin. 2005, 43, 289-386.
[5] Gao, F.; Li, Y.Y.; Wang, D.; Huang, X.; Liu, Q. Molecules. 2012, 17, 5187-5194.
[6] Dasyukevich, O.I.; Solyanik, G.I. Exp. Oncol. 2007, 29, 317-319.
[7] Garmanchouk, L.V.; Pyaskovskaya, O.N.; Yanish, Y.V.; Shlyakhovenko, V.A.; Dasyukevich, O.I.; Solyanik, G.I. Exp. Oncol. 2005, 27, 262-266.
[8] Xu, X.F.; Chen, Y.H.; Wang, J.; Liao, J.J.; Wu, J.H. J. Chin. Med. Mater. 2010, 33, 1909-1912.
[9] Wada, K.; Hazawa, M.; Takahashi, K.; Mori, T.; Kawahara, N.; Kashiwakura, I. J. Nat. Med. 2011, 65, 43-49.
[10] Xu, Y.; Guo, Z.J.; Wu, N. Fitoterapia. 2010, 81, 1091-1093.
[11] de Inés, C.; Reina, M.; Gavín, J.A.; González-Coloma, A.Z. Naturforsch. C. 2006, 61, 11-18.
[12] Wada, K.; Hazawa, M.; Takahashi, K.; Mori, T.; Kawahara, N.; Kashiwakura, I. J. Nat. Prod. 2007, 70, 1854-1858.
[13] Hazawa, M.; Takahashi, K.; Wada, K.; Mori, T.; Kawahara, N.; Kashiwakura, I. Invest. New Drugs. 2011, 29, 1-8.
[14] Hazawa, M.; Wada, K.; Takahashi, K.; Mori, T.; Kawahara, N.; Kashiwakura, I. Invest. New Drugs. 2009, 27, 111-119.
[15] Hazawa, M.; Wada, K.; Kashiwakura, I. Phytother. Res. 2012, 26, 1262-1264.
[16] Zhou, S.J.; Du, G.Y. Chin. J. Chin. Mater. Med. 2003, 28, 910-913.
[17] Wang, L.; Zhang, D.; Qu, X.; Zhang, Z.; Wang, Y. Chin. J. Chin. Mater. Med. 2009, 34, 596-599.
[18] Liu, X.X.; Jian, X.X.; Cai, X.F.; Chao, R.B.; Chen, Q.H.; Chen, D.L.; Wang, X.L.; Wang, F.P. Chem. Pharm. Bull. 2012, 60, 144-149.
[19] Fan, X.; Chen, Y.; Xing, J.; Wu, P.; Chen, H.; Yang, J.; Zhang, J.; Wang, X.; Huang, C. J. Ethnopharmacol. 2012, 139, 42-51.
[20] Huang, X.; Yang, Y.; Zhu, J.; Xu, D.; Peng, J.; Liu, J. J. Cardiovasc. Pharmacol. 2012, 59, 77-83.
[21] Liang, Y.; Zhu, J.; Yang, Y.M.; Li, J.D.; Sun, Y.; Guan, J.; Gao, X.; Li, C.R.; Tang, Y. Chin. J. Cardiol. 2006, 34, 1035-1039.
[22] Lin, J.S.; Chan, C.Y.; Yang, C.; Wang, Y.H.; Chiou, H.Y.; Su, Y.C. Exp. Biol. Med. 2007, 232, 557-564.
[23] Yamada, K.; Suzuki, E.; Nakaki, T.; Watanabe, S.; Kanba, S. J. Ethnopharmacol. 2005, 96, 165-169.

[24] Chan, T.Y. Clin. Toxicol. 2009, 47, 279-285.
[25] Forgo, P.; Borcsa, B.; Csupor, D.; Fodor, L.; Berkecz, R.; Molnár, V.A.; Hohmann, J. Planta Med. 2011, 77, 368-373.
[26] Li, Y.; Tu, D.; Xiao, H.; Du, Y.; Zou, A.; Liao, Y.; Dong, S. J. Ethnopharmacol. 2010, 131, 187-195.
[27] Wada, K.; Nihira, M.; Hayakawa, H.; Tomita, Y.; Hayashida, M.; Ohno, Y. Forensic Sci. Int. 2005, 148, 21-29.
[28] Liou, S.S.; Liu, I.M.; Lai, M.C.; Cheng, J.T. J. Ethnopharmacol. 2005, 99, 379-383.
[29] Wu, G.; Huang, W.; Zhang, H.; Li, Q.; Zhou, J.; Shu, H. J. Ethnopharmacol. 2011, 136, 254-259.
[30] Xu, H.; Arita, H.; Hayashida, M.; Zhang, L.; Sekiyama, H.; Hanaoka, K. J. Ethnopharmacol. 2006, 103, 392-397.
[31] Shu, H.; Hayashida, M.; Arita, H.; Huang, W.; Xiao, L.; Chiba, S.; Sekiyama, H.; Hanaoka, K. J. Ethnopharmacol. 2008, 119, 276-283.
[32] Shu, H.; Hayashida, M.; Huang, W.; An, K.; Chiba, S.; Hanaoka, K.; Arita, H. J. Ethnopharmacol. 2008, 117, 158-165.
[33] Wang, C.F.; Gerner, P.; Wang, S.Y.; Wang, G.K. Anesthesio-logy. 2007, 107, 82-90.
[34] Wang, C.F.; Gerner, P.; Schmidt, B.; Xu, Z.Z.; Nau, C.; Wang, S.Y.; Ji, R.R.; Wang, G.K. Anesth. Analg. 2008, 107, 1397-1405.
[35] Wang, D.P.; Lou, H.Y.; Huang, L.; Hao, X.J.; Liang, G.Y.; Yang, Z.C.; Pan, W.D. Bioorg. Med. Chem. Lett. 2012, 22, 4444-4446.
[36] Jiang, B.; Lin, S.; Zhu, C.; Wang, S.; Wang, Y.; Chen, M.; Zhang, J.; Hu, J.; Chen, N.; Yang, Y.; Shi, J. J. Nat. Prod. 2012, 75, 1145-1159.
[37] Wang, J.L.; Shen, X.L.; Chen, Q.H.; Qi, G.; Wang, W.; Wang, F.P. Chem. Pharm. Bull. 2009, 57, 801-807.
[38] Bello-Ramírez, A.M.; Nava-Ocampo, A.A. Fundam. Clin. Pharmacol. 2004, 18, 157-161.
[39] Zhao, Y.; Bu, Q.; Zhou, Y.; Lv, L.; Yan, G.; Chen, B.; Wang, L.; Cen, X. Neurotoxicology. 2010, 31, 752-757.
[40] Turabekova, M.A.; Rasulev, B.F.; Dzhakhangirov, F.N.; Leszczynska, D.; Leszczynski, J. Eur. J. Med. Chem. 2010, 45, 3885-3894.
[41] Borcsa, B.; Widowitz, U.; Csupor, D.; Forgo, P.; Bauer, R.; Hohmann, J. Fitoterapia. 2011, 82, 365-368.
[42] Nesterova, IuV.; Povet'eva, T.N.; Aksinenko, S.G.; Suslov, N.I.; Gaĭdamovich, N.N.; Nagorniak, IuG.; Popova, E.V.; Kravtsova, S.S.; Andreeva, T.I. Vestn. Ross. Akad. Med. Nauk. 2009, 11, 30-34.
[43] Pashinskiĭ, V.G.; Gaĭdamovich, N.N.; Povet'eva, T.N.; Vetoshkina, T.V.; Nesterova, IuV.; Pushkarskiĭ, S.V. Eksp. Klin. Farmakol. 2006, 69, 55-57.
[44] Sun, K.; Yang, J.; Shen, D.K. Chin. Acupunct. Moxib. 2008, 28, 87-90.
[45] Xu, L.L.; Wang, L.; Wang, Y.Q. Chin. J. Integr. Tradit. West. Med. 2006, 26, S102-S107.
[46] Yu, H.; Ji, X.; Wu, Z.; Wang, S. Chin. J. Chin. Mater. Med. 2011, 36, 2535-2538.
[47] de la Peña, S.S.; Sothern, R.B.; López, F.S.; Lujambio, I.M.; Waizel-Bucay, J.; Sánchez, C.O.; Monroy, C.P.; Betancourt, E.T. Pharmacogn. Mag. 2011, 7, 234-242.
[48] Chen, T.T.; Qi, C.; Guo, H.; Cheng, Z.; Zhou, D.; Liu, H.; Liu, J. J. Acupunct. Meridian. Stud. 2009, 2, 71-74.
[49] Wada, K.; Nihira, M.; Ohno, Y. J. Ethnopharmacol. 2006, 105, 89-94.
[50] Wangchuk, P.; Bremner, J.B.; Skelton, B.W.; White, A.H.; Rattanajak, R.; Kamchonwongpaisan, S. J. Ethnopharmacol. 2010, 130, 559-562.
[51] Yuan, C.L.; Wang, X.L. Nat. Prod. Res. 2012, 26, 2099-2102.
[52] Liu, Z.L.; Cao, J.; Zhang, H.M.; Lin, L.L.; Liu, H.J.; Du, S.S.; Zhou, L.; Deng, Z.W. J. Agric. Food Chem. 2011, 59, 3701-3706.
[53] Ahmad, M.; Ahmad, W.; Ahmad, M.; Zeeshan, M.; Shaheen, F. J. Enzyme Inhib. Med. Chem. 2008, 23, 1018-1022.
[54] Nesterova, Y.V.; Povetieva, T.N.; Suslov, N.I.; Semenov, A.A.; Pushkarskiy, S.V. Bull. Exp. Biol. Med. 2011, 151, 425-428.

[55] Song, M.K.; Liu, H.; Jiang, H.L.; Yue, J.M.; Hu, G.Y.; Chen, H.Z. Neuroscience. 2008, 155, 469-475.
[56] Xiao, K.; Wang, L.; Liu, Y.; Peng, C.; Yan, G.; Zhang, J.; Zhuo, Y.; Li, H. Birth Defects Res. B. Dev. Reprod. Toxicol. 2007, 80, 208-212.
[57] Xiao, K.; Yan, G.Y.; Wang, L.; Liu, Y.Q.; Peng, C.; Duan, J.C.; Fu, Z.T.; Li, H.X. J. Sichuan Univ (Med. Sci. Edition). 2008, 39, 441-444.
[58] Ge, Y.; Mu, S.; Zhang, J.; Wang, Y.; Sun, Q.; Hao, X. Chin. J. Chin. Mater. Med. 2009, 34, 1935-1937.
[59] Bai, G.; Yang, Y.; Shi, Q.; Liu, Z.; Zhang, Q.; Zhu, Y.Y. Acta Pharmcol. Sin. 2008, 29, 1187-1194.
[60] Nisar, M.; Ahmad, M.; Wadood, N.; Lodhi, M.A.; Shaheen, F.; Choudhary, M.I. J. Enzyme Inhib. Med. Chem. 2009, 24, 47-51.
[61] Liou, S.S.; Liu, I.M.; Lai, M.C. J. Ethnopharmacol. 2006, 106, 256-262.
[62] Wu, L.; Gao, X.; Wang, L.; Liu, Q.; Fan, X.; Wang, Y.; Cheng, Y. Chin. J. Chin. Mater. Med. 2011, 36, 2907-2910.
[63] Lin, G.M.; Liu, L.; Shao, W. J. Zhejiang Univ. Sci. B. 2011, 12, 563-567.
[64] Gao, T.; Ma, S.; Song, J.; Bi, H.; Tao, Y. Int. J. Biol. Macromol. 2011, 49, 580-586.
[65] Gao, T.; Bi, H.; Ma, S.; Lu, J. Int. J. Biol. Macromol. 2010, 46, 85-90.
[66] Lu, Y.; Bu, H.; Yang, L.; Li, X.; Li, F. Chin. J. Chin. Mater. Med. 2011, 36, 1154-1157.
[67] Gao, T.; Bi, H.; Ma, S.; Lu, J. Nat. Prod. Commun. 2010, 5, 447-455.
[68] Zhao, C.; Li, M.; Luo, Y.; Wu, W. Carbohydr. Res. 2006, 341, 485-491.
[69] Dong, L.F.; Zhang, Y.J.; Liu, J.S.; Song, S.X.; Hou, J.; Lu, Z.J. Chin. J. Cell. Mol. Immunol. 2006, 22, 458-462.
[70] Huang, X.; Tang, J.; Zhou, Q.; Lu, H.; Wu, Y.; Wu, W. Lipids Health Dis. 2010, 9, 9.
[71] Yan, H.C.; Qu, H.D.; Sun, L.R.; Li, S.J.; Cao, X.; Fang, Y.Y.; Jie, W.; Bean, J.C.; Wu, W.K.; Zhu, X.H.; Gao, T.M. Int. J. Neuropsychopharmacol. 2010, 13, 623-633.
[72] Park, K.H.; Park, M.; Choi, S.E.; Jeong, M.S.; Kwon, J.H.; Oh, M.H.; Choi, H.K.; Seo, S.J.; Lee, M.W. Biol. Pharm. Bull. 2009, 32, 2029-2033.
[73] Shrestha, B.B.; Dall'Acqua, S.; Gewali, M.B.; Jha, P.K.; Innocenti, G. Carbohydr. Res. 2006, 341, 2161-2165.
[74] Luis, J.C.; Valdés, F.; Martín, R.; Carmona, A.J.; Díaz, J.G. Fitoterapia. 2006, 77, 469-471.
[75] Vitalini, S.; Braca, A.; Passarella, D.; Fico, G. Fitoterapia. 2010, 81, 940-947.
[76] Mariani, C.; Braca, A.; Vitalini, S.; De Tommasi, N.; Visioli, F.; Fico, G. Phytochemistry. 2008, 69, 1220-1226.
[77] Makino, T.; Kato, K.; Mizukami, H. Biol. Pharm. Bull. 2009, 32, 1741-1748.
[78] Qu, W.X.; Mou, Z.L.; Cui, H.Y.; Zhang, Z.Q. Phytochem. Anal. 2011, 22, 199-204.
[79] Xiao, P.G.; Chen, D.H.; Song, W.L. Acta Phytotaxon. Sin. 1984, 22, 53-56.
[80] Wang, W.T. Aconitum L. In: Flora Reipublicae Popularis Sinicae. Beijing: Science Press. 1979, 27, 113-362.
[81] Pan, A.H.; Liu, J. J. Forensic Med. 2005, 21, 118-120.
[82] Qiao, Y.L.; Zhang, Y.H.; Zhang, W.; Zhang, J.L. J. AOAC. Int. 2009, 92, 653-662.
[83] Sun, A.; Gao, B.; Ding, X.; Huang, C.M.; But, P.P. J. Anal. Methods Chem. 2012, 2012, 936131.
[84] Wang, Z.; Wen, J.; Xing, J.; He, Y. J. Pharm. Biomed. Anal. 2006, 40, 1031-1034.
[85] Kang, X.Q.; Fan, Z.C.; Zhang, Z.Q. J. Chromatogr. Sci. 2010, 48, 860-865.
[86] Zhao, Y.Y.; Zhang, Y.; Lin, R.C.; Sun, W.J. Fitoterapia. 2009, 80, 333-338.
[87] Wang, X.; Wang, H.; Zhang, A.; Lu, X.; Sun, H.; Dong, H.; Wang, P. J. Proteome Res. 2012, 11, 1284-1301.
[88] Hao, D.C.; Xiao, P.G.; Peng, Y.; Liu, M.; Huo, L. Acta Pharm. Sin. 2012, 47, 827-835.
[89] Hao, D.C.; Gu, X.J.; Xiao, P.G.; Peng, Y. Chin. J. Nat. Med. 2012, In press.
[90] Zhang, F.M.; Ge, S.; Chen, W.L. Acta Phytotaxon. Sin. 2003, 41, 220-228.
[91] He, J.; Wong, K.L.; Shaw, P.C.; Wang, H.; Li, D.Z. Planta Med. 2010, 76, 1622-1628.
[92] Wang, L.; Abbott, R.J.; Zheng, W.; Chen, P.; Wang, Y.; Liu, J. Mol. Ecol. 2009, 18, 709-721.
[93] Zhang, F.M.; Chen, W.L.; Yang, Q.E.; Ge, S. Plant Syst. Evol. 2005, 254, 39-48.
[94] Luo, Q.; Ma, D.W.; Wang, Y.H. Chin. Tradit. Herb. Drug. 2006, 37, 1554-1557.
[95] Zhang, F.M.; Kong, H.Z.; Ge, S. Biochem. Genet. 2003, 41, 47-55.
[96] Hao, D.C.; Ge, G.B.; Xiao, P.G.; Zhang, Y.Y.; Yang, L. PLoS One. 2011, 6, e21220.
[97] Hao, D.C.; Yang, L.; Xiao, P.G. Mol. Genet. Genomics. 2011, 285, 197-205.
[98] Shen, Y.; Ai, H.L.; Zi, S.H.; Wang, J.J.; Zhang, X.M.; Chen, J.J. J. Asian Nat. Prod. Res. 2012, 14, 244-248.
[99] Kurtoğlu, S.; Sen, B.; Melikoğlu, G.; Becker, H.; Zapp, J.; Kiemer, A.K.; Meriçli, F.; Meriçli, A.H. Z. Naturforsch. C. 2012, 67, 103-107.
[100] Mu, Z.Q.; Gao, H.; Huang, Z.Y.; Feng, X.L.; Yao, X.S. Org. Lett. 2012, 14, 2758-2761.
[101] Xu, N.; Zhao, D.F.; Liang, X.M.; Zhang, H.; Xiao, Y.S. Molecules. 2011, 16, 3345-3350.
[102] Yang, L.J.; Luo, Y.P.; Chen, W.; Zhao, J.F.; Yang, X.D.; Li, L. J. Asian Nat. Prod. Res. 2009, 11, 728-731.
[103] Lin, L.; Chen, D.L.; Liu, X.Y.; Chen, Q.H.; Wang, F.P.; Yang, C.Y. Nat. Prod. Commun. 2009, 4, 897-901.
[104] Li, Y.; Liang, S. Chin. J. Chin. Mater. Med. 2009, 34, 1220-1222.
[105] He, P.; Jian, X.X.; Chen, D.L.; Wang, F.P. Nat. Prod. Commun. 2009, 4, 19-22.
[106] Csupor, D.; Forgo, P.; Wenzig, E.M.; Bauer, R.; Hohmann, J. J. Nat. Prod. 2008, 71, 1779-1782.
[107] He, Y.Q.; Ma, Z.Y.; Yang, Q.; Yao, B.H.; Gao, L.M. Acta Pharm. Sin. 2008, 43, 934-937.
[108] Tang, Q.; Liu, J.; Xue, J.; Ye, W.; Zhang, Z.; Yang, C. J. Chromatogr. B. 2008, 872, 181-185.