Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders and is also responsible for more than half of all dementia cases. In our ongoing efforts to identify promising phytoco Show more
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders and is also responsible for more than half of all dementia cases. In our ongoing efforts to identify promising phytocompounds as potential modulators of AD-related molecular targets, we studied 53 phytocompounds from Bergenia ciliata, a medicinal plant known for its in vivo anti-Alzheimer activity. Acetylcholinesterase (AChE), GSK-3β, and β-site amyloid precursor protein cleaving enzyme (BACE1) were the target proteins. Molecular docking and 100 ns molecular dynamics (MD) simulations revealed that 3-O-galloylcatechin and 3-O-galloylepicatechin showed favorable interactions with AChE and GSK-3β, as they were able to outperform the positive controls in all of the studied parameters. However, the MM-GBSA binding free energy calculations revealed that only 3-O-galloylepicatechin, but not 3-O-galloylcatechin, outperformed the positive control of GSK-3β. Density functional theory (DFT) studies revealed that 3-O-galloylcatechin and 3-O-galloylepicatechin were stable and chemically reactive at the active sites of AChE and GSK-3β. The in-silico findings suggest that the observed in-vivo anti-Alzheimer activity of B. ciliata may be partly associated with the favorable molecular interactions of 3-O-galloylcatechin and 3-O-galloylepicatechin with AChE and GSK-3β. The current findings highlight the structural and mechanistic relevance of B. ciliata phytocompounds in modulating AD-associated targets. Based on the current findings, medicinal plants that contain 3-O-galloylcatechin and 3-O-galloylepicatechin may also be screened for their interactions with AD-related molecular targets. Show less