Antiepileptic geissoschizine methyl ether is an inhibitor of multiple neuronal channels
文献类型：期刊论文
| 作者 | Xie, Zhu-qing1,2,3; Tian, Xiao-ting3; Zheng, Yue-ming3; Zhan, Li3; Chen, Xue-qin3; Xin, Xiao-ming1,2; Huang, Cheng-gang3 ; Gao, Zhao-bing3
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2020-01-07 |
| 页码 | 9 |
| 关键词 | geissoschizine methyl ether Uncaria rhynchophyll antiepileptic drug hippocampal neurons action potential nicotinic acetylcholine receptors voltage-gated ion channels mouse seizure model |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-019-0327-4 |
| 通讯作者 | Xin, Xiao-ming(xinxm@sumhs.edu.cn) ; Huang, Cheng-gang(cghuang@simm.ac.cn) ; Gao, Zhao-bing(zbgao@simm.ac.cn) |
| 英文摘要 | Geissoschizine methyl ether (GM) is an indole alkaloid isolated from Uncaria rhynchophyll (UR) that has been used for the treatment of epilepsy in traditional Chinese medicine. An early study in a glutamate-induced mouse seizure model demonstrated that GM was one of the active ingredients of UR. In this study, electrophysiological technique was used to explore the mechanism underlying the antiepileptic activity of GM. We first showed that GM (1-30 mu mol/L) dose-dependently suppressed the spontaneous firing and prolonged the action potential duration in cultured mouse and rat hippocampal neurons. Given the pivotal roles of ion channels in regulating neuronal excitability, we then examined the effects of GM on both voltage-gated and ligand-gated channels in rat hippocampal neurons. We found that GM is an inhibitor of multiple neuronal channels: GM potently inhibited the voltage-gated sodium (Na-V), calcium (Ca-V), and delayed rectifier potassium (I-K) currents, and the ligand-gated nicotinic acetylcholine (nACh) currents with IC50 values in the range of 1.3-13.3 mu mol/L. In contrast, GM had little effect on the voltage-gated transient outward potassium currents (I-A) and four types of ligand-gated channels (gamma-amino butyric acid (GABA), N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainite (AMPA/KA receptors)). The in vivo antiepileptic activity of GM was validated in two electricity-induced seizure models. In the maximal electroshock (MES)-induced mouse seizure model, oral administration of GM (50-100 mg/kg) dose-dependently suppressed generalized tonic-clonic seizures. In 6-Hz-induced mouse seizure model, oral administration of GM (100 mg/kg) reduced treatment-resistant seizures. Thus, we conclude that GM is a promising antiepileptic candidate that inhibits multiple neuronal channels. |
| WOS关键词 | NICOTINIC ACETYLCHOLINE-RECEPTORS ; UNCARIA-RHYNCHOPHYLLA ; INDOLE ALKALOIDS ; ION CHANNELS ; EPILEPSY ; POTENT ; IDENTIFICATION ; LEVETIRACETAM ; HIPPOCAMPUS ; MECHANISMS |
| 资助项目 | National Science Fund for Distinguished Young Scholars[81825021] ; Personalized Medicines Molecular Signature-Based Drug Discovery and Development (Strategic Priority Research Program of the Chinese Academy of Sciences)[XDA12040221] ; Personalized Medicines Molecular Signature-Based Drug Discovery and Development (Strategic Priority Research Program of the Chinese Academy of Sciences)[XDA15050308] ; National Natural Science Foundation of China[81603096] ; National Natural Science Foundation of China[81773707] ; National Natural Science Foundation of China[61433017] ; Shanghai Municipal Science and Technology Major Project[2018SHZDZX01] ; ZJ Lab |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000508161000001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/282372]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xin, Xiao-ming; Huang, Cheng-gang; Gao, Zhao-bing |
| 作者单位 | 1.Shanghai Univ Med & Hlth Sci, Shanghai 201318, Peoples R China 2.Shanghai Univ Tradit Chinese Med, Grad Sch, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xie, Zhu-qing,Tian, Xiao-ting,Zheng, Yue-ming,et al. Antiepileptic geissoschizine methyl ether is an inhibitor of multiple neuronal channels[J]. ACTA PHARMACOLOGICA SINICA,2020:9. |
| APA | Xie, Zhu-qing.,Tian, Xiao-ting.,Zheng, Yue-ming.,Zhan, Li.,Chen, Xue-qin.,...&Gao, Zhao-bing.(2020).Antiepileptic geissoschizine methyl ether is an inhibitor of multiple neuronal channels.ACTA PHARMACOLOGICA SINICA,9. |
| MLA | Xie, Zhu-qing,et al."Antiepileptic geissoschizine methyl ether is an inhibitor of multiple neuronal channels".ACTA PHARMACOLOGICA SINICA (2020):9. |
入库方式： OAI收割
来源：上海药物研究所
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