A Computational Approach for Exploring Herbal Inhibitors of Acetylcholinesterase in Alzheimer's Disease

Alzheimers Disease (AD) is the most common type of age related dementia in the world. Many hypotheses shed light on several reasons that lead to AD development. The cholinergic hypothesis describes that the destruction of an essential neurotransmitter, acetylcholine (AChE) by acetylcholinesterase (AChE) enzyme, leads to the AD onset. The hydrolysis of acetylcholine by excess amount of AChE decreases the amount of acetylcholine in the brain, thus interfering with the normal brain functions. Many anti-AChE agents can be used to treat AD by targeting AChE. In our study, 14 anti-AChE agents from plants: 1,8-cineol, berberine, carvacrol, cheilanthifoline, coptisine, estragole, harmaline, harmine, liriodenine, myrtenal, naringenin, protopine, scoulerine, stylopine were tested against AChE and compared with two controls: donepezil and galantamine, using different techniques of molecular docking. Molecular docking study was conducted for all the 14 selected ligands against AChE to identify the best three ligands among them. To determine the safety and efficacy of the three best ligands, a set of tests like the druglikeness property test, ADME/T test, PASS & P450 site of metabolism prediction, pharmacophore mapping and modelling and DFT calculations were performed. In our experiment, berberine, coptisine and naringenin were determined as the three ligands from the docking study. Further analysis of these 3 ligands showed coptisine as the most potent anti-AChE agent. The molecular dynamics simulation study showed quite good stability of the coptisine-AChE docked complex. Administration of berberine, coptisine and naringenin might be potential treatments for AD.