Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP/PS1 transgenic mice and scopolamine-induced memory impairment mice
文献类型：期刊论文
| 作者 | He, Dandan; Wu, Hui; Wei, Yue; Liu, Wei; Huang, Fei; Shi, Hailian; Zhang, Beibei; Wu, Xiaojun; Wang, Changhong |
| 刊名 | European journal of pharmacology
 |
| 出版日期 | 2015-12-05 |
| 卷号 | 768页码:96-107 |
| ISSN号 | 1879-0712 |
| DOI | 10.1016/j.ejphar.2015.10.037 |
| 文献子类 | Article |
| 英文摘要 | Harmine, a β-carboline alkaloid present in Peganum harmala with a wide spectrum of pharmacological activities, has been shown to exert strong inhibition against acetylcholinesterase in vitro. However, whether it can rescue the impaired cognition has not been elucidated yet. In current study, we examined its effects on scopolamine-induced memory impairment mice and APP/PS1 transgenic mice, one of the models for Alzheimer's disease, using Morris Water Maze test. In addition, whether harmine could penetrate blood brain barrier, interact with and inhibit acetylcholinesterase, and activate downstream signaling network was also investigated. Our results showed that harmine (20mg/kg) administered by oral gavage for 2 weeks could effectively enhance the spatial cognition of C57BL/6 mice impaired by intraperitoneal injection of scopolamine (1mg/kg). Meanwhile, long-term consumption of harmine (20mg/kg) for 10 weeks also slightly benefited the impaired memory of APP/PS1 mice. Furthermore, harmine could pass through blood brain barrier, penetrate into the brain parenchyma shortly after oral administration, and modulate the expression of Egr-1, c-Jun and c-Fos. Molecular docking assay disclosed that harmine molecule could directly dock into the catalytic active site of acetylcholinesterase, which was partially confirmed by its in vivo inhibitory activity on acetylcholinesterase. Taken together, all these results suggested that harmine could ameliorate impaired memory by enhancement of cholinergic neurotransmission via inhibiting the activity of acetylcholinesterase, which may contribute to its clinical use in the therapy of neurological diseases characterized with acetylcholinesterase deficiency. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/266471]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wu, Xiaojun; Wang, Changhong |
| 作者单位 | The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China |
| 推荐引用方式 GB/T 7714 | He, Dandan,Wu, Hui,Wei, Yue,et al. Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP/PS1 transgenic mice and scopolamine-induced memory impairment mice[J]. European journal of pharmacology,2015,768:96-107. |
| APA | He, Dandan.,Wu, Hui.,Wei, Yue.,Liu, Wei.,Huang, Fei.,...&Wang, Changhong.(2015).Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP/PS1 transgenic mice and scopolamine-induced memory impairment mice.European journal of pharmacology,768,96-107. |
| MLA | He, Dandan,et al."Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP/PS1 transgenic mice and scopolamine-induced memory impairment mice".European journal of pharmacology 768(2015):96-107. |
入库方式： OAI收割
来源：上海药物研究所
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