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结合基于 1H-NMR 的代谢组学和网络药理学剖析慢性不可预知轻度应激诱导抑郁小鼠中对美丽崖豆藤抗抑郁作用的机制。

Combining 1H-NMR-based metabonomics and network pharmacology to dissect the mechanism of antidepression effect of Milletia speciosa Champ on mouse with chronic unpredictable mild stress-induced depression.

机构信息

Pharmaceutical College, Guangxi Medical University, Nanning, China.

Guangxi Yuhualing Technology Development Co. LTD, Nanning, China.

出版信息

J Pharm Pharmacol. 2021 Jun 8;73(7):881-892. doi: 10.1093/jpp/rgaa010.

Abstract

OBJECTIVES

Milletia speciosa Champ (MS), a traditional Chinese medicine, has the abilities of antistress, antifatigue, anti-oxidation and so on. In our previous study, MS was found to antidepression while the underlying mechanism of which needs further elucidation.

METHODS

Here, a proton nuclear magnetic resonance (1H-NMR)-based metabonomics combined network pharmacology research approach was performed to investigate the antidepressive mechanism of MS act on mouse with chronic unpredictable mild stress-induced depression.

KEY FINDINGS

Results showed that MS could alleviate the ethology of depression (including sucrose preference degree, crossing lattice numbers and stand-up times) and disordered biochemical parameters (5-hydroxytryptamine, norepinephrine and brain-derived neurotrophic factor). Metabonomics study and network pharmacology analysis showed that MS might improve depression through synergistically regulating five targets including Maoa, Maob, Ache, Ido1 and Comt, and three metabolic pathways such as tryptophan metabolism, synthesis of neurotransmitter and phospholipid metabolism.

CONCLUSIONS

This study for the first time preliminary clarified the potential antidepressive mechanism of MS and provided theoretical basis for developing MS into novel effective antidepressant.

摘要

目的

牡荆素(MS)是一种传统的中药,具有抗应激、抗疲劳、抗氧化等作用。在我们之前的研究中,发现 MS 具有抗抑郁作用,但具体的作用机制仍需进一步阐明。

方法

采用基于质子核磁共振(1H-NMR)的代谢组学结合网络药理学研究方法,研究 MS 对慢性不可预测轻度应激诱导抑郁小鼠的抗抑郁作用机制。

主要发现

结果表明,MS 可缓解抑郁的行为学(包括蔗糖偏好度、穿越格子数和站立时间)和生化参数紊乱(5-羟色胺、去甲肾上腺素和脑源性神经营养因子)。代谢组学研究和网络药理学分析表明,MS 可能通过协同调节包括 Maoa、Maob、Ache、Ido1 和 Comt 在内的 5 个靶点和色氨酸代谢、神经递质合成和磷脂代谢等 3 条代谢途径来改善抑郁。

结论

本研究首次初步阐明了 MS 的潜在抗抑郁作用机制,为将 MS 开发成新型有效的抗抑郁药提供了理论依据。

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