Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice

doi:10.1038/aps.2015.111

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	Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice
	Zhang, Qi; Guo, Fei; Fu, Zhi-wen; Zhang, Bing; Huang, Cheng-gang; Li, Yang
刊名	ACTA PHARMACOLOGICA SINICA
	2016-02
卷号	37 期号:2 页码:166-176
关键词	Rhizoma Anemarrhenae timosaponin YY-23 depression NMDA receptor antagonist chronic mild stress chronic social defeat stress fluoxetine
ISSN号	1671-4083
DOI	10.1038/aps.2015.111
文献子类	Article
英文摘要	Aim: N-methyl-D-aspartic acid (NMDA) receptor modulators have shown promising results as potential antidepressant agents, whereas timosaponins extracted from the Chinese herb Rhizoma Anemarrhenae exhibit antidepressant activities. In the present study we examined whether YY-23, a modified metabolite of timosaponin B-III, could affect NMDA receptors in rat hippocampal neurons in vitro, and evaluated its antidepressant-like effects in stressed mice. Methods: NMDA-induced currents were recorded in acutely dissociated rat hippocampal CA1 neurons using a whole-cell recording technique. C57BL/6 mice were exposed to a 6-week chronic mild stress (CMS) or a 10-d chronic social defeat stress (CSDS). The stressed mice were treated with YY-23 (20 mg.kg(-1).d(-1)) or a positive-control drug, fluoxetine (10 mg.kg(-1).d(-1)) for 3 weeks. Behavioral assessments were carried out every week. Results: In acutely dissociated rat hippocampal CA1 neurons, YY-23 selectively and reversibly inhibited NMDA-induced currents with an EC50 value of 2.8 mu mol/L. This inhibition of NMDA-induced currents by YY-23 was non-competitive, and had no features of voltage dependency or use-dependency. Treatment of the stressed mice with YY-23 not only reversed CMS-induced deficiency of sucrose preference and immobility time, and CSDS-induced reduction of social interaction, but also had faster onset as compared to fluoxetine. Conclusion: YY-23 is a novel non-competitive antagonist of NMDA receptors with promising rapid antidepressant-like effects in mouse models of CMS and CSDS depression.
资助项目	National Natural Science Foundation[31128009] ; National Natural Science Foundation[31171011] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2014ZX09102-001-005] ; Ministry of Science and Technology[2013CB910601]
WOS关键词	CHRONIC MILD STRESS ; D-ASPARTATE ANTAGONIST ; SOCIAL DEFEAT STRESS ; MAJOR DEPRESSIVE DISORDER ; ANIMAL-MODELS ; HUPERZINE-A ; KETAMINE ; MEMANTINE ; BEHAVIOR ; MK-801
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000370677100004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276158]
专题	上海中药现代化研究中心药物质量控制与固体化学研究中心药理学第二研究室药物安全性评价中心
通讯作者	Huang, Cheng-gang; Li, Yang
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Qi,Guo, Fei,Fu, Zhi-wen,et al. Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice[J]. ACTA PHARMACOLOGICA SINICA,2016,37(2):166-176.
APA	Zhang, Qi,Guo, Fei,Fu, Zhi-wen,Zhang, Bing,Huang, Cheng-gang,&Li, Yang.(2016).Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice.ACTA PHARMACOLOGICA SINICA,37(2),166-176.
MLA	Zhang, Qi,et al."Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice".ACTA PHARMACOLOGICA SINICA 37.2(2016):166-176.