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从丹参中分离出的抗抑郁和抗焦虑化合物与血清素类药物相互作用。

Antidepressant and anxiolytic compounds isolated from Salvia elegans interact with serotonergic drugs.

机构信息

Centro de Investigación Biomédica del Sur, Instituto Mexicano del Seguro Social (IMSS), Argentina 1, 62790, Xochitepec, Morelos, México.

Doctorado en Ciencias Biológicas Y de La Salud, División de Ciencias Biológicas Y de La Salud, Universidad Autónoma Metropolitana (UAM), México City, México.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2021 Dec;394(12):2419-2428. doi: 10.1007/s00210-021-02155-6. Epub 2021 Sep 27.

DOI:10.1007/s00210-021-02155-6
PMID:34568977
Abstract

Salvia elegans belongs to a genus plants with biological activities in central nervous system. In this work, the purpose was to evaluate the anxiolytic and antidepressant effects of fractions and compounds isolated from S. elegans and its interaction with serotoninergic drugs by using behavioral tests in mice. Fractions from aerial parts of S. elegans were obtained by column chromatography, SeF1, SeF2, SeF3, and SeF4. Each of them was administered to 25 mg/k in ICR mice subject to forced swimming test (FST), or elevated plus maze test (EPM), or open field test (OFT). The most active fractions were chemically separated until compounds, which were analyzed as anxiolytic or antidepressant and the coadministration of these treatments with 5-HT and 5-HT drugs was measured in the different biological tests. All fractions were anxiolytic and antidepressant, oleanolic acid (OA) was found in SeF2, and from SeF3, a mixture of terpenes was found; a GC-MS analysis confirmed the presence of two main compounds: rosifoliol and agaraspirol (TM, mixture of terpenes). TM (doses-response curve, 0.01, 0.1, 0.5, 1.0, and 2.0 mg/kg) and OA (5 mg/kg) were also evaluated demonstrating an antidepressant and anxiolytic effect, respectively. The combination of TM (0.5 mg/kg) with 8-OH (selective 5-HT receptor agonist) induced an increment of antidepressant activity, while with the antagonist WAY-100635, the effect diminished. But with DOI (5-HTc/5-HT receptor agonist), there was no change, and with KET (5-HT receptor antagonist), the activity was increased. When OA is co-administered with 8-OH or with DOI, the anxiolytic activity of this terpene, diminished; but with the combination with antagonists, the effect of OA shows no change. TM and OA were antidepressant and anxiolytic, respectively, on mice exposed to different tests, and these are able to interact with serotoninergic drugs.

摘要

墨旱莲属植物具有中枢神经系统的生物活性。本工作旨在通过小鼠行为学试验评估墨旱莲地上部分提取物及化合物的抗焦虑和抗抑郁作用及其与 5-羟色胺能药物的相互作用。用柱层析法从墨旱莲地上部分得到 SeF1、SeF2、SeF3 和 SeF4 等 4 个部位。将它们分别以 25mg/kg 给 ICR 小鼠灌胃,然后进行强迫游泳试验(FST)、高架十字迷宫试验(EPM)或旷场试验(OFT)。活性最强的部位经进一步化学分离得到化合物,分析其抗焦虑和抗抑郁作用,并在不同的生物学试验中观察这些化合物与 5-HT 和 5-HT 能药物联合给药的作用。所有的部位都有抗焦虑和抗抑郁作用,在 SeF2 中发现了齐墩果酸(OA),在 SeF3 中发现了一种混合萜类化合物;GC-MS 分析证实存在两种主要化合物:罗沙醇和阿加瑞罗(TM,混合萜类)。TM(剂量-反应曲线,0.01、0.1、0.5、1.0 和 2.0mg/kg)和 OA(5mg/kg)也进行了评价,分别表现出抗抑郁和抗焦虑作用。TM(0.5mg/kg)与 8-OH(5-HT 受体选择性激动剂)联合使用可增强抗抑郁作用,而与拮抗剂 WAY-100635 联合使用则降低了作用。但与 DOI(5-HTc/5-HT 受体激动剂)联合使用没有变化,与 KET(5-HT 受体拮抗剂)联合使用则增强了作用。当 OA 与 8-OH 或 DOI 联合使用时,这种萜类化合物的抗焦虑活性降低;但与拮抗剂联合使用时,OA 的作用没有变化。TM 和 OA 分别对暴露于不同试验的小鼠具有抗抑郁和抗焦虑作用,并且它们能够与 5-羟色胺能药物相互作用。

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本文引用的文献

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The therapeutic role of 5-HT1A and 5-HT2A receptors in depression.5-羟色胺1A和5-羟色胺2A受体在抑郁症中的治疗作用。
J Psychiatry Neurosci. 2004 Jul;29(4):252-65.
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The use of a plus-maze to measure anxiety in the mouse.使用加迷宫来测量小鼠的焦虑水平。
Psychopharmacology (Berl). 1987;92(2):180-5. doi: 10.1007/BF00177912.