ⅣMep⁃S as a novel dual⁃binding AChEI to ameliorate scopolamine⁃induced learning and memory impairment in mice
10.19405/j.cnki.issn1000-1492.2023.01.005
- Author:
Wenzhe Dong
1
,
2
;
Wei Zheng
3
;
Juan Li
4
Author Information
1. Basic Medical College of Shanghai University of Medicine &
2. Health Sciences , Shanghai 201318
3. NPFPC Key Laboratory of Contraceptives and Devices , Shanghai Institute of Planned Parenthood Research , Shanghai 200032
4. Dept ofPharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine , Shanghai 200025
- Publication Type:Journal Article
- Keywords:
Alzheimer ′s disease;
dual⁃binding AChE inhibitor;
molecular docking;
learning and memory impair⁃ment
- From:
Acta Universitatis Medicinalis Anhui
2023;58(1):22-27
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To explore the effect of ( - ) Ⅳmeptazinol⁃serotonin hybrid , [( - ) ⅣMep⁃S] on scopolamineinduced learning and memory impairment in mice.
Methods:The binding of ( - ) ⅣMep⁃S and hAChE was analyzed by molecular docking. The effect of ( - ) ⅣMep⁃S on AChE activity was observed in vivo and in vitro. The effect of ( - ) ⅣMep⁃S on learning and memory impairment induced by scopolamine was examined in Morris water maze test in mice. The effect of ( - ) ⅣMep⁃S on the motor behaviors of mice was detected by open field test.
results:Molecular docking analysis revealed that ( - ) ⅣMep⁃S binded to human AChE. In parallel , ( - ) ⅣMep⁃S overtly inhibited the activity of AChE derived from mouse forebrain and SH⁃SY5Y neuronal cells , and IC50 values were lower than those of the positive control drug rivastigmine. In the Morris water maze test , mice treated with ( - ) ⅣMep⁃S (2. 5 mg/kg) showed significantly reduced latency on day 4 (P < 0. 05) . Moreover, they exhibited significantly greater percentage of distance travelled and percentage of time spent in the target quadrant in the probe trial on day 5 (P < 0. 05) . ( - ) ⅣMep⁃S at 0. 5 mg/kg did not show any significant effects. In addition , ( - ) Ⅳ Mep⁃S inhibited the enhancement of forebrain AChE activity induced by scopolamine (P < 0. 05) . The open field test showed that the effect of ( - ) ⅣMep⁃S on scopolamine⁃induced learning and memory impairment was not due to the difference on the motor behaviors of mice.
Conclusion:( - ) ⅣMep⁃S can effectively inhibit AChE activity and ameliorate scopolamineinduced learning and memory impairment in mice.
- Full text:2024070419165207520新型双配基AChEI美普色...小鼠学习记忆功能障碍的研究_董文哲.pdf
