钩吻的化学成分及药理作用研究进展
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摘要
钩吻Gelsemium elegans,马钱科Loganiaceae钩吻属Gelsemium常绿木质藤本植物,为中国传统药用植物,其味辛、苦,性温,有剧毒,常用来祛风、攻毒、消肿和止痛。该文检索并查阅了近些年来钩吻在化学成分和药理作用方面的文献,并对其进行总结和归纳。目前的研究表明,已从钩吻中分离出生物碱、环烯醚萜、三萜类、酚酸类、甾体类、香豆素、木脂素、四甲基环己烯型单萜苷类化合物、黄酮类等多种成分,其中,钩吻生物碱多为吲哚类生物碱,是其主要的活性成分,能显著抑制中枢神经活动。现代药理学研究表明钩吻生物碱具有多种药理活性,可通过调控细胞周期来达到抗肿瘤的目的;增强巨噬细胞吞噬能力,保护白细胞,促进机体免疫调节;治疗癌性疼痛和长期疼痛;使心肌收缩力减弱,血管舒张以达到降压效果;另外还对焦虑症和皮肤病的治疗起到一定作用。在今后的研究中,仍需对钩吻的化学成分进行深入研究,开发有前景的先导化合物,并进一步明确毒理和药理临床价值,探明作用机制,使其得到更充分合理的利用,为钩吻扩大应用和安全使用奠定基础。
Gelsemium elegans,the evergreen woody vine of the genus Gelsemium of the Loganiaceae family in China,is a traditional Chinese medicinal plant. It is spicy,bitter,warm,highly toxic and commonly used for dispelling wind-evil, attacking poison, reducing swelling and relieving pain. In this article, the researches on the chemical constituents and pharmacological effects of G. elegans in recent years were retrieved,reviewed and summarized. So far, alkaloids, iridoids, triterpenes, phenolic acids, steroids, coumarins,lignans,megastigmane glycosides and other ingredients have been separated from G. elegans. Alkaloids,mostly of indole alkaloids,are the main active ingredients there of which can significantly inhibit central nervous activity.Modern pharmacological studies have shown that alkaloids have a variety of pharmacological activities,which can achieve the purpose of anti-tumor by regulating cell cycle; enhance macrophage phagocytosis,protect white blood cells, and promote immune regulation; relieve cancer pain and long-term pain; reduce the myocardial contractility,get vasodilation to achieve antihypertensive effect; and also play an important role in the treatment of anxiety disorder and dermatosis. In the future research on G. elegans,it is still necessary to further study the chemical constituents,develop promising lead compounds,conduct in-depth research on its toxicology and clinical pharmacology,and clarify its mechanism of action, make it used more fully and reasonably, and lay the foundation for the application and safe use of G. elegans.
Gelsemium elegans,the evergreen woody vine of the genus Gelsemium of the Loganiaceae family in China,is a traditional Chinese medicinal plant. It is spicy,bitter,warm,highly toxic and commonly used for dispelling wind-evil, attacking poison, reducing swelling and relieving pain. In this article, the researches on the chemical constituents and pharmacological effects of G. elegans in recent years were retrieved,reviewed and summarized. So far, alkaloids, iridoids, triterpenes, phenolic acids, steroids, coumarins,lignans,megastigmane glycosides and other ingredients have been separated from G. elegans. Alkaloids,mostly of indole alkaloids,are the main active ingredients there of which can significantly inhibit central nervous activity.Modern pharmacological studies have shown that alkaloids have a variety of pharmacological activities,which can achieve the purpose of anti-tumor by regulating cell cycle; enhance macrophage phagocytosis,protect white blood cells, and promote immune regulation; relieve cancer pain and long-term pain; reduce the myocardial contractility,get vasodilation to achieve antihypertensive effect; and also play an important role in the treatment of anxiety disorder and dermatosis. In the future research on G. elegans,it is still necessary to further study the chemical constituents,develop promising lead compounds,conduct in-depth research on its toxicology and clinical pharmacology,and clarify its mechanism of action, make it used more fully and reasonably, and lay the foundation for the application and safe use of G. elegans.
引文
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[5]周名璐,杨兴业,熊志刚,等.钩吻总碱注射液对麻醉大鼠呼吸、血压、心电及脑电的影响[J].中成药,1996(6):24-26.
[6] Beljanski M,Beljanski M S. Selective inhibition of in vitro synthesis of cancer DNA by alkaloids ofβ-carboline class[J]. Exp Cell Biol,1982,50(2):79-87.
[7]王智华,张和岑.中药钩吻的生药学研究[J].上海第一医学院学报,1982(2):81-86.
[8] Kitajima M,Kogure N,Yamaguchi K,et al. Structure reinvestigation of gelsemoxonine, a constituent of Gelsemium elegans,reveals a novel azetidine-containing indole alkaloid[J]. Org Lett,2003,5(12):2075-2078.
[9]韩海斌.钩吻化学成分及生药学研究[D].沈阳:沈阳药科大学,2007.
[10] Kogure N,Ishii N,Kitajima M,et al. Four novel gelsenicine-related oxindole alkaloids from the leaves of Gelsemium elegans Benth[J]. Org Lett,2006,8(14):3085-3088.
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[12] Yamada Y,Kitajima M,Kogure N,et al. Seven new monoterpenoid indole alkaloids from Gelsemium elegans[J]. Chem Asian J,2011,6(1):166-173.
[13] Ponglux D,Wongseripipatana S,Subhadhirasakul S,et al. Studies on the indole alkaloids of Gelsemium elegans,(Thailand):structure elucidation and proposal of biogenetic route[J]. Tetrahedron,1988,44(16):5075-5094.
[14] YIN S,HE X F,WU Y,et al. Monoterpenoid indole alkaloids bearing an N4-Iridoid from Gelsemium elegans[J]. Chem Asian J,2008,3(10):1824-1829.
[15] ZHANG Z,ZHANG Y,WANG Y H,et al. Three novelβ-carboline alkaloids from Gelsemium elegans[J].Fitoterapia,2012,83(4):704-708.
[16] Ponglux D,Wongseripipatana S,Takayama H,et al. A new class of indole alkaloid‘elegansamine’constructed from a monoterpenoid indole alkaloid and an iridoid[J].Tetrahedron Lett,1988,29(42):5395-5396.
[17] SUN M X,HOU X L,GAO H H,et al. Two new koumine-type indole alkaloids from Gelsemium elegans Benth[J]. Molecules,2013,18(2):1819-1825.
[18] ZHAO Q C,HUA W,ZHANG L,et al. Antitumor activity of two gelsemine metabolites in rat liver microsomes[J].J Asian Nat Prod Res,2010,12(9):731-739.
[19] Yamada Y,Kitajima M,Kogure N,et al. Four novel gelsedine-type oxindole alkaloids from Gelsemium elegans[J]. Tetrahedron,2008,64(33):7690-7694.
[20] ZHANG Z,DI Y T,WANG Y H,et al. Gelegamines AE:five new oxindole alkaloids from Gelsemium elegans[J]. Tetrahedron,2009,65(23):4551-4556.
[21] ZHANG B F,CHOU G X,WANG Z T. Two new 11-hydroxy-substituted gelsedine-type indole alkaloids from the stems of Gelsemium elegans[J]. Helv Chim Acta,2009,92(9):1889-1894.
[22] XU Y K,YANG S P,LIAO S G,et al. Alkaloids from Gelsemium elegans[J]. J Nat Prod,2006,69(9):1347-1350.
[23] OUYANG S,WANG L,ZHANG Q W,et al. Six new monoterpenoid indole alkaloids from the aerial part of Gelsemium elegans[J]. Tetrahedron,2011,67(26):4807-4813.
[24] LIN L Z,Cordell G A,NI C Z,et al. Gelsamydine,an indole alkaloid from Gelsemium elegans with two monoterpene units[J]. J Org Chem,1989,54(13):3199-3202.
[25] LIN L Z,HU S F,Cordell G A. 19α-hydroxygelsamydine from Gelsemium elegans[J]. Phytochemistry,1996,43(3):723-726.
[26] LIN L Z,Cordell G A,NI C Z,et al. Two oxindole alkaloids from Gelsemium elegans[J]. Phytochemistry,1990,29(9):3013-3017.
[27] XU Y K,LIAO S G,NA Z,et al. Gelsemium alkaloids,immunosuppressive agents from Gelsemium elegans[J].Fitoterapia,2012,83(6):1120-1124.
[28] Yamada Y,Kitajima M,Kogure N,et al. Spectroscopic analyses and chemical transformation for structure elucidation of two novel indole alkaloids from Gelsemium elegans[J]. Tetrahedron Lett,2009,50(26):3341-3344.
[29]金浩崙,徐任生.钩吻生物碱的研究——钩吻素戊的结构[J].化学学报,1982,40(12):1129-1135.
[30] LIN L Z,Yeh S,Cordell G A,et al. Three oxindole alkaloids from Gelsemium species[J]. Phytochemistry,1991,30(2):679-683.
[31]张秋萍,张彬锋,侴桂新,等.钩吻地上部分的化学成分[J].中国中药杂志,2011,36(10):1305-1310.
[32] LIN L Z,Cordell G A,NI C Z,et al. New humanteninetype alkaloids from Gelsemium elegans[J]. J Nat Prod,1989,52(3):588-594.
[33] YANG J S,CHEN Y W. Elucidation of the structures of humantenine and humantenirine[J]. Acta Pharm Sin,1984,19(9):686-690.
[34] Kogure N,Kobayashi H,Ishii N,et al. New humanteninetype indole alkaloids with iridoid unit from Gelsemium species[J]. Tetrahedron Lett,2008,49(22):3638-3642.
[35] LIN L Z,Cordell G A,Ni C Z,et al. Gelsemamide and11-methoxygelsemamide,two novel secoindole alkaloids from Gelsemium elegans[J]. Tetrahedron Lett,1989,30(10):1177-1180.
[36] LIN L Z,Cordell G A,NI C Z,et al. Oxindole alkaloids from Gelsemium elegans[J]. Phytochemistry,1991,30(4):1311-1315.
[37]崔研,孙铭学,高焕焕,等.钩吻根脂溶性化学成分的分离与鉴定[J].沈阳药科大学学报,2014,31(4):248-251,324.
[38] LIN L Z,Cordell G A,NI C Z,et al. 19-(R)-and 19-(S)-hydroxydihydrokoumine from Gelsemium elegans[J]. Phytochemistry,1990,29(3):965-968.
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