DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice
Deficiency of the cholinergic system is thought to play a vital role in cognitive impairment of dementia. DL0410 was discovered as a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinestease (BuChE), with potent efficiency in in-vitro experiments, but its in vivo effect on the cholinerg...
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doaj-fb68b20a86af4c58b12309881f06e8232020-11-24T20:51:06ZengMDPI AGMolecules1420-30492017-03-0122341010.3390/molecules22030410molecules22030410DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in MiceWenwen Lian0Jiansong Fang1Lvjie Xu2Wei Zhou3De Kang4Wandi Xiong5Hao Jia6Ai-Lin Liu7Guan-Hua Du8Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xian Nong Tan Street, Beijing 100050, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xian Nong Tan Street, Beijing 100050, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xian Nong Tan Street, Beijing 100050, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xian Nong Tan Street, Beijing 100050, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xian Nong Tan Street, Beijing 100050, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xian Nong Tan Street, Beijing 100050, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xian Nong Tan Street, Beijing 100050, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xian Nong Tan Street, Beijing 100050, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xian Nong Tan Street, Beijing 100050, ChinaDeficiency of the cholinergic system is thought to play a vital role in cognitive impairment of dementia. DL0410 was discovered as a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinestease (BuChE), with potent efficiency in in-vitro experiments, but its in vivo effect on the cholinergic model has not been evaluated, and its action mechanism has also not been illustrated. In the present study, the capability of DL0410 in ameliorating the amnesia induced by scopolamine was investigated, and its effect on the cholinergic system in the hippocampus and its binding mode in the active site of AChE was also explored. Mice were administrated DL0410 (3 mg/kg, 10 mg/kg, and 30 mg/kg), and mice treated with donepezil were used as a positive control. The Morris water maze, escape learning task, and passive avoidance task were used as behavioral tests. The test results indicated that DL0410 could significantly improve the learning and memory impairments induced by scopolamine, with 10 mg/kg performing best. Further, DL0410 inhibited the AChE activity and increased acetylcholine (ACh) levels in a dose-dependent manner, and interacted with the active site of AChE in a similar manner as donepezil. However, no difference in the activity of BuChE was found in this study. All of the evidence indicated that its AChE inhibition is an important mechanism in the anti-amnesia effect. In conclusion, DL0410 could be an effective therapeutic drug for the treatment of dementia, especially Alzheimer’s disease.http://www.mdpi.com/1420-3049/22/3/410alzheimer’s diseaseDL0410AChE inhibitorBuChE inhibitorACh |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wenwen Lian Jiansong Fang Lvjie Xu Wei Zhou De Kang Wandi Xiong Hao Jia Ai-Lin Liu Guan-Hua Du |
spellingShingle |
Wenwen Lian Jiansong Fang Lvjie Xu Wei Zhou De Kang Wandi Xiong Hao Jia Ai-Lin Liu Guan-Hua Du DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice Molecules alzheimer’s disease DL0410 AChE inhibitor BuChE inhibitor ACh |
author_facet |
Wenwen Lian Jiansong Fang Lvjie Xu Wei Zhou De Kang Wandi Xiong Hao Jia Ai-Lin Liu Guan-Hua Du |
author_sort |
Wenwen Lian |
title |
DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice |
title_short |
DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice |
title_full |
DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice |
title_fullStr |
DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice |
title_full_unstemmed |
DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice |
title_sort |
dl0410 ameliorates memory and cognitive impairments induced by scopolamine via increasing cholinergic neurotransmission in mice |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2017-03-01 |
description |
Deficiency of the cholinergic system is thought to play a vital role in cognitive impairment of dementia. DL0410 was discovered as a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinestease (BuChE), with potent efficiency in in-vitro experiments, but its in vivo effect on the cholinergic model has not been evaluated, and its action mechanism has also not been illustrated. In the present study, the capability of DL0410 in ameliorating the amnesia induced by scopolamine was investigated, and its effect on the cholinergic system in the hippocampus and its binding mode in the active site of AChE was also explored. Mice were administrated DL0410 (3 mg/kg, 10 mg/kg, and 30 mg/kg), and mice treated with donepezil were used as a positive control. The Morris water maze, escape learning task, and passive avoidance task were used as behavioral tests. The test results indicated that DL0410 could significantly improve the learning and memory impairments induced by scopolamine, with 10 mg/kg performing best. Further, DL0410 inhibited the AChE activity and increased acetylcholine (ACh) levels in a dose-dependent manner, and interacted with the active site of AChE in a similar manner as donepezil. However, no difference in the activity of BuChE was found in this study. All of the evidence indicated that its AChE inhibition is an important mechanism in the anti-amnesia effect. In conclusion, DL0410 could be an effective therapeutic drug for the treatment of dementia, especially Alzheimer’s disease. |
topic |
alzheimer’s disease DL0410 AChE inhibitor BuChE inhibitor ACh |
url |
http://www.mdpi.com/1420-3049/22/3/410 |
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