A Computational Study of Natural Compounds from Bacopa monnieri in the Treatment of Alzheimer's Disease.

Keeping in view the public health-related issues of Alzheimer's disease (AD), its unpredictable occurrence and progression indicate the needs for best treatment options. The present bioinformatics study explores the binding pattern and molecular interactions between human acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes with natural compounds from Bacopa monnieri. The docking analysis between natural compounds as a ligand and AChE, BuChE as a receptor was completed using MGL tools Autodock 4.2 module. The analysis of the hydrophobic interactions, inhibition constants, and hydrogen bonds may indicates that they play a significant role in finding out the interacting position at the active site. However, after analyzing the binding energy (ΔG), the documented data shows that bacoside X, bacoside A, 3-beta-D-glucosylstigmasterol and daucosterol could be good inhibitors in the inhibition of AChE and BuChE activities. Therefore, our study indicates that the inhibition constants of the aforesaid natural compounds of Bacopa can be utilized for the development of inhibitors.

In Silico Analysis of Green Tea Polyphenols as Inhibitors of AChE and BChE Enzymes in Alzheimer's Disease Treatment.

Alzheimer's disease (AD) is the most frequent cause of dementia, especially in the elderly. AD is the most common progressive neurodegenerative disorder, which involves the loss of structure and function of cholinergic neurons. Moreover, if these neuronal changes cannot be compensated, this may ultimately lead to neurodegenerative processes. Therefore, most of the drug therapies are based on the cholinergic hypothesis, which suggests that AD begins as a deficiency in the production of the neurotransmitter acetylcholine. In this context, many inhibitors play an important role in AD treatment among which acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have more potential in the treatment process of AD. In this study, we selected tea polyphenols of green tea which are reported as AChE and BChE inhibitors used in the treatment of AD. The molecular docking results revealed that polyphenols exhibit interactions and inhibit by binding with AChE and BChE. The amount of energy to bind with AChE and BChE needed by Epigallocatechin-3-gallate was lowest at about -14.45 and -13.30 kcal/mol, respectively. All compounds showed binding energy values ranging between -14.45 to -9.75 kcal/mol for both types of enzymes. The present docking study suggests that tea polyphenols inhibit AChE as well as BChE and enhance the cholinergic neurotransmission by prolonging the time. However, AChE molecules remain in the synaptic cleft. In consideration to these findings, cholinesterase inhibitors are suggested as the standard drugs for the treatment of AD.