Next Article in Journal
The Role of Sub- and Supercritical CO2 as “Processing Solvent” for the Recycling and Sample Preparation of Lithium Ion Battery Electrolytes
Next Article in Special Issue
Cholinesterase Inhibitory Activities of Adamantyl-Based Derivatives and Their Molecular Docking Studies
Previous Article in Journal
Metabolite Profiling of Eastern Teaberry (Gaultheria procumbens L.) Lipophilic Leaf Extracts with Hyaluronidase and Lipoxygenase Inhibitory Activity
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Molecules 2017, 22(3), 410; doi:10.3390/molecules22030410

DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice

1
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xian Nong Tan Street, Beijing 100050, China
2
Beijing Key Laboratory of Drug Target Research and Drug Screening, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
3
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
*
Authors to whom correspondence should be addressed.
Academic Editors: Anthony H. Futerman, Yacov Ashani and Gabriel Amitai
Received: 19 December 2016 / Accepted: 3 March 2017 / Published: 6 March 2017
View Full-Text   |   Download PDF [3300 KB, uploaded 9 March 2017]   |  

Abstract

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. View Full-Text
Keywords: alzheimer’s disease; DL0410; AChE inhibitor; BuChE inhibitor; ACh alzheimer’s disease; DL0410; AChE inhibitor; BuChE inhibitor; ACh
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Lian, W.; Fang, J.; Xu, L.; Zhou, W.; Kang, D.; Xiong, W.; Jia, H.; Liu, A.-L.; Du, G.-H. DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice. Molecules 2017, 22, 410.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top