The inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit on acetylcholinesterase: A interaction, kinetic, spectroscopic, and molecular simulation study

This study aimed to investigate the inhibition mechanism of polyphenols from PEF on AChE. Results showed that myricetin, quercetin, fisetin, and gallic acid were the most active components because of their strong inhibition ability on AChE. Combination of the four compounds manifested a synergistic effect on AChE in mixed−type inhibition. These inhibitors quenched the intrinsic fluorescence of AChE through a static quenching mechanism and induced enzyme secondary structure changes. In addition, all the four docked polyphenol−AChE complexes were relatively stable during the whole simulation process. [Display omitted] •Phyllanthus emblica Linn. fruit (PEF) is rich in polyphenols.•The inhibition mechanism of PEF polyphenols on AChE was studied.•Myricetin, quercetin, fisetin, gallic acid were the most active components in PEF.•Four polyphenols showed synergistic effect on AChE at the selected concentration.•PEF polyphenols quenched AChE fluorescence and induced AChE conformation changes.•Hydrogen bonds and hydrophobic interactions were important for the interaction. The present study aimed to investigate the inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit (PEF, family Euphorbiaceous) on acetylcholinesterase (AChE). Interaction assay, enzyme kinetics, spectroscopic methods, and molecular simulations were performed. Results showed that myricetin, quercetin, fisetin, and gallic acid were the most active components in PEF, because of their low docking scores and strong inhibition ability on AChE with IC50 values of 0.1974 ± 0.0047, 0.2589 ± 0.0131, 1.0905 ± 0.0598 and 1.503 ± 0.0728 mM, respectively. Among them, the results of kinetic study showed that myricetin, quercetin, and fisetin reversibly inhibited AChE in a competitive manner, while gallic acid inhibited it through a noncompetition type. The interaction assay implied that a combination of the four polyphenols at the selected concentrations manifested a synergistic inhibition effect on AChE in a mixed inhibition type. Fluorescence and UV-vis spectrophotometry revealed that the active PEF polyphenols could strongly quench the intrinsic fluorescence of AChE via a static quenching mechanism. Circular dichroism spectroscopy analysis indicated that the active PEF polyphenols gave rise to the secondary structure changes of AChE by increasing the content of α-helix and reducing β-sheet and random coil conformation. The molecular dynamics simulation results validated that all the four dock