Linarin improves the dyskinesia recovery in Alzheimer's disease zebrafish by inhibiting the acetylcholinesterase activity
| Autor: | Wang Yangyang, Longhu Wang, Yueting Cao, Keke Cui, Jinghui Zhang, Yongjiang Wu, Hongye Pan |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Drug medicine.drug_class Aché media_common.quotation_subject Pharmacology 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Pathogenesis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Alzheimer Disease medicine Animals Glycosides General Pharmacology Toxicology and Pharmaceutics Donepezil Zebrafish media_common Binding Sites Dyskinesias Dose-Response Relationship Drug biology Recovery of Function General Medicine biology.organism_classification Acetylcholinesterase language.human_language Molecular Docking Simulation 030104 developmental biology chemistry Acetylcholinesterase inhibitor Dyskinesia language Female Cholinesterase Inhibitors medicine.symptom medicine.drug |
| Zdroj: | Life Sciences. 222:112-116 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2019.02.046 |
| Popis: | Background Due to complex pathogenesis of Alzheimer's disease (AD), currently there is no effective disease-modifying treatment. Acetylcholinesterase (AChE) has introduced itself as an important target for AD therapy. Linarin as the representative active ingredient of flavonoid glycoside in Flos chrysanthemi indici has been found to have anti-acetylcholinesterase effect. Aims The present study intended to explore the potential effect of linarin for treatment of AD. Main methods In this study, molecular docking simulation was used to evaluate whether linarin could dock with AChE and decipher the mechanism of linarin as an AChE inhibitor. After molecular docking simulation, AlCl3-induced Alzheimer's disease zebrafish model was established. Effects of linarin on treating AD zebrafish dyskinesia and AChE inhibition were compared with donepezil (DPZ) which was used as a positive control drug. Key findings Molecular docking simulation showed that linarin plays a critical role in AChE inhibition by binding AChE active sites. The experiments illustrated that the dyskinesia recovery rate of AD zebrafish could be significantly improved by linarin. The dyskinesia recovery and AChE inhibition rate were 88.0% and 74.5% respectively, while those of DPZ were 79.3% and 43.6%. Significance These findings provide evidences for supporting linarin to be developed into an AD drug by inhibiting the activity of AChE. |
| Databáze: | OpenAIRE |
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