钩藤通过激活 5-HT 受体改善不可预知慢性轻度应激诱导的小鼠抑郁：转录组学的见解。
Uncaria rhynchophylla ameliorates unpredictable chronic mild stress-induced depression in mice via activating 5-HT receptor: Insights from transcriptomics.
机构信息
Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine, College of Pharmacy, College of Integrative Medicine, Department of Neurosurgery, The First and Second Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China.
State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
出版信息
Phytomedicine. 2021 Jan;81:153436. doi: 10.1016/j.phymed.2020.153436. Epub 2020 Dec 7.
BACKGROUND
Depression is a pervasive or persistent mental disorder that causes mood, cognitive and memory deficits. Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history, although its efficacy and potential mechanism are still uncertain.
PURPOSE
The present study aimed to investigate anti-depression effect and potential mechanism of U. rhynchophylla extract (URE).
STUDY DESIGN AND METHODS
A mouse depression model was established using unpredictable chronic mild stress (UCMS). Effects of URE on depression-like behaviours, neurotransmitters, and neuroendocrine hormones were investigated in UCMS-induced mice. The potential target of URE was analyzed by transcriptomics and bioinformatics methods and validated by RT-PCR and Western blot. The agonistic effect on 5-HT receptor was assayed by dual-luciferase reporter system.
RESULTS
URE ameliorated depression-like behaviours, and modulated levels of neurotransmitters and neuroendocrine hormones, including 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), corticosterone (CORT), corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH), in UCMS-induced mice. Transcriptomics and bioinformatics results indicated that URE could regulate glutamatergic, cholinergic, serotonergic, and GABAergic systems, especially neuroactive ligand-receptor and cAMP signaling pathways, revealing that Htr1a encoding 5-HT receptor was a potential target of URE. The expression levels of downstream proteins of 5-HT signaling pathway 5-HT, CREB, BDNF, and PKA were increased in UCMS-induced mice after URE administration, and URE also displayed an agonistic effect against 5-HT receptor with an EC value of 17.42 μg/ml.
CONCLUSION
U. rhynchophylla ameliorated depression-like behaviours in UCMS-induced mice through activating 5-HT receptor.
背景
抑郁症是一种普遍或持续存在的精神障碍，会导致情绪、认知和记忆缺陷。钩藤在长期以来被广泛用于治疗中枢神经系统疾病，尽管其疗效和潜在机制仍不确定。
目的
本研究旨在探讨钩藤提取物（URE）的抗抑郁作用及其潜在机制。
研究设计和方法
采用不可预测性慢性轻度应激（UCMS）建立小鼠抑郁模型。在 UCMS 诱导的小鼠中，研究了 URE 对抑郁样行为、神经递质和神经内分泌激素的影响。采用转录组学和生物信息学方法分析 URE 的潜在靶点，并通过 RT-PCR 和 Western blot 进行验证。通过双荧光素酶报告系统检测 URE 对 5-HT 受体的激动作用。
结果
URE 改善了抑郁样行为，并调节了 UCMS 诱导的小鼠神经递质和神经内分泌激素的水平，包括 5-羟色胺（5-HT）、5-羟吲哚乙酸（5-HIAA）、多巴胺（DA）、3,4-二羟基苯乙酸（DOPAC）、高香草酸（HVA）、皮质酮（CORT）、促肾上腺皮质激素释放激素（CRH）和促肾上腺皮质激素（ACTH）。转录组学和生物信息学结果表明，URE 可以调节谷氨酸能、胆碱能、血清素能和 GABA 能系统，特别是神经活性配体-受体和 cAMP 信号通路，表明编码 5-HT 受体的 Htr1a 是 URE 的潜在靶点。在 URE 给药后，UCMS 诱导的小鼠中 5-HT 信号通路的下游蛋白 5-HT、CREB、BDNF 和 PKA 的表达水平增加，URE 对 5-HT 受体也表现出激动作用，EC 值为 17.42μg/ml。
结论
钩藤通过激活 5-HT 受体改善 UCMS 诱导的小鼠抑郁样行为。
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