Linarin improves the dyskinesia recovery in Alzheimer's disease zebrafish by inhibiting the acetylcholinesterase activity

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.