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[白屈菜和博落回中分离出的生物碱及其衍生药物对肝脏线粒体单胺氧化酶活性的抑制作用]

[Inhibition of liver mitochondrial monoamine oxidase activity by alkaloids isolated from Chelidonium and Macleaya and by their derivative drugs].

作者信息

Iagodina O V, Nikol'skaia E B, Faddeeva M D

机构信息

I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg.

出版信息

Tsitologiia. 2003;45(10):1032-7.

Abstract

It has been shown that the major alkaloids from plants Chelidonium majus L. and Macleaya (Bocconia) cordata and microcarpa, namely, berberine, sanguinarine, chelidonine, and drugs "Ukrain" (thiophosphoric acid derivative of a sum of the alkaloids isolated from Ch. majus L.) and "Sanguirythrine" (a mixture of the alkaloids sanguinarine and chelerythrine, w/w 3:7, isolated from Macleaya), are irreversible inhibitors of oxidative deamination reaction of serotonin and tyramine as substrates, catalyzed by rat liver mitochondrial monoamine oxidase (MAO). At the same time these substances do not influence the oxidative deamination reaction of benzylamine as substrate (in concentration 1 mM or less). The substrate specificity of this inhibition manifests that mainly the oxidative deamination reactions catalyzed by MAO form A are inhibited by the agents studied. Among the examined agents, alkaloid chelidonine and drug "Ukrain" are the strongest inhibitors of the reaction. Alkaloids berberine and sanguinarine and drug "Sanguirythrine" exhibit a weaker action. Judging from the data obtained, sanguinarine and chelerythrine appear to exert similar inhibitory effects in this reaction, since sanguinarine and "Sanguirythrine" have similar values of bimolecular rate constants of their interaction with mitochondrial MAO. As it is well known, the MAO inhibitors appear to be, as a rule, pronounced antidepressants. The combination of malignotoxicity and antidepressive activity in drug "Ukrain" seems to be favourable for its clinical applications.

摘要

业已表明,白屈菜(Chelidonium majus L.)、博落回(Macleaya (Bocconia) cordata)及小果博落回(Macleaya microcarpa)植物中的主要生物碱,即黄连素、血根碱、白屈菜碱,以及药物“乌头碱”(从白屈菜中分离出的生物碱总和的硫代磷酸衍生物)和“血根红碱”(从博落回中分离出的血根碱和白屈菜红碱的混合物,重量比为3:7),是大鼠肝脏线粒体单胺氧化酶(MAO)催化的以血清素和酪胺为底物的氧化脱氨反应的不可逆抑制剂。同时,这些物质在浓度为1 mM或更低时,不影响以苄胺为底物的氧化脱氨反应。这种抑制作用的底物特异性表明,所研究的试剂主要抑制由MAO A型催化的氧化脱氨反应。在所检测的试剂中,生物碱白屈菜碱和药物“乌头碱”是该反应最强的抑制剂。生物碱黄连素和血根碱以及药物“血根红碱”的作用较弱。从所得数据判断,血根碱和白屈菜红碱在该反应中似乎发挥相似的抑制作用,因为血根碱和“血根红碱”与线粒体MAO相互作用的双分子速率常数相似。众所周知,MAO抑制剂通常似乎是显著的抗抑郁药。药物“乌头碱”的恶性毒性和抗抑郁活性的结合似乎有利于其临床应用。

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