Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice
文献类型：期刊论文
| 作者 | Zhang, Qi; Guo, Fei; Fu, Zhi-wen; Zhang, Bing; Huang, Cheng-gang ; Li, Yang
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| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 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. |
| 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 |
| 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研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000370677100004 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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