Arbutin aids in the recovery of dyskinesia in Alzheimer's zebrafish by decreasing the function of acetylcholinesterase

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by oxidative stress, neuroinflammation and decreased levels of neurotransmitters (acetylcholine). AD is a complex pathogenesis disease; currently, no efficient drugs are available to treat Alzheimer’s disease. Several AD drug targets have been identified for the last two decades including acetylcholinesterase (AchE), beta-secretase, gamma-secretase and monoamine oxidase. Most of the FDA-approved drugs are acetylcholinesterase inhibitors. Hence acetylcholinesterase is an important drug target for AD. Arbutin is the active glycosylated hydroquinone with acetylcholinesterase (AChE) inhibitory property isolated from the Arctostaphylos uvaursi. Our current aim is to explore arbutin's anti- Alzheimer’s potential. In this study, molecular docking simulations were done with various AD targets to assess the anti-Alzheimer’s possibilities of arbutin. Furthermore, the zebrafish AD model was established with the help of aluminium chloride (AlCl3). Anti- Alzheimer’s efficiency and dyskinesia potentials of arbutin were assessed with the arbutin-treated zebrafish compared with the positive control drug Rivastigmine. Results of molecular docking simulations exhibited that arbutin plays a crucial role in Alzheimer’s disease progression. Arbutin significantly increased the dyskinesia recovery in the AD zebrafish model and it can be developed into an AD drug by inhibiting the acetylcholinesterase and other AD targets.