DOI: 10.1002/ame2.12126
Evodiamine derivatives improve cognitive abilities in APPswe/PS1ΔE9 transgenic mouse models of Alzheimer's disease
Shuo Pang1
Caixian Sun1
Shan Gao1
Yajun Yang2
Xiandao Pan2
Lianfeng Zhang1
1.Key Laboratory of Human Disease Comparative Medicine,National Health Commission of China (NHC),Institute of Laboratory Animal Science,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing,China;Beijing Engineering Research Center for Experimental Animal Models of Human Diseases,Institute of Laboratory Animal Science,Peking Union Medical College,Chinese Academy of Medical Science2.Beijing Key Laboratory of Active Substance Discovery and Drug ability Evaluation Institute of Material Medical,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China
摘要：Background:Alzheimer's disease (AD) is a complex neurodegenerative disease.Due to the complexity of its molecular pathogenesis and the interaction of the numerous factors involved,the etiology and pathogenesis of AD have not been fully elucidated.Therefore,effective treatment for AD remains to be developed.Evodiamine,a quinolone alkaloid,has been found to improve learning and memory ability to in the APPswe/PS1△E9 mouse model of dementia.However,the cytotoxic-ity and physicochemical properties of evodiamine have limited its use in the treat-ment of AD.Methods:Evodiamine and its derivatives were effectively synthesized by EDCI-mediated condensation at room temperature.These target compounds contained 1 thio- and 21 oxo-evodiamine derivatives with different substituted groups.The cytotoxicity of evodiamine and its derivatives and the neuroprotective effects of the evodiamine derivatives against H2O2-induced cell loss in SH-SY5Y cells were investi-gated using the WST-8 assay.The Morris water-maze test was used to detect the ef-fect of evodiamine and its derivatives on improving learning and memory in APPswe/PS1△E9 mice.Results:In this study,a series of oxo- and thio-evodiamine derivatives was synthe-sized.Several derivatives showed lower cytotoxicity and stronger neuroprotective effects than evodiamine and elicited enhanced cognitive improvement,especially in the test of spatial memory in APPswe/PS1△E9 mice.Conclusion:Our study provides insights for developing novel evodiamine derivatives for chemical intervention and treatment of AD.
机标关键词：
论文发表日期：2020-06-25
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：7( 193-199 )
英文信息