Cited by 69Cholinesterase and Neurodegenerative DiseasesEnzyme function and inhibitionBioactive natural compounds

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

Wu, Min, Liu, Ming, Wang, Feiyang, Cai, Jianhang, Luo, Qingying, Li, Shanshan, Zhu, Junxiang, Tang, Zizhong +3 more·2022·Food Research International

Abstract

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 IC 50 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 docked polyphenol-AChE complexes were relatively stable according to their root-mean-square distance, root-mean-square fluctuations, solvent accessible surface area, radius of gyration values and hydrogen bonds evaluations during the whole simulation process. Overall, our study provides a creative insight into the further utilization of PEF polyphenols as functional components in exploring natural AChE inhibitors.

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Crossref · 10.1016/j.foodres.2022.111497

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Authors
Wu, M., Liu, M., Wang, F., Cai, J., Luo, Q., Li, S., Zhu, J., Tang, Z., Fang, Z., Wang, C., & Chen, H.
Affiliations
  • Sichuan Agricultural University (CN)
  • Qingdao Agricultural University (CN)
Corresponding author
  • Luo, Qingying
  • Chen, Hong
Venue
Food Research International
Publisher
Elsevier BV
Published
2022-08
Volume
158
Pages
111497
ISSN
0963-9969 (ISSN-L)
OpenAlex
W4282004391
Cited by
69
References
33
Citations by year
2026: 14 · 2025: 17 · 2024: 18 · 2023: 17 · 2022: 3
FWCI
8.25
Type
journal article
Language
en
Open access
closed
Locations
  • Food Research International (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81903284)
Topics
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioactive natural compounds
Keywords
Phyllanthus emblica, acetylcholinesterase inhibition, polyphenols, myricetin, quercetin, fisetin, gallic acid, competitive inhibition, mixed-type inhibition, synergistic inhibition, fluorescence quenching, protein secondary structure, molecular docking, molecular dynamics simulation
MeSH terms
Acetylcholinesterase, Fruit, Gallic Acid, Kinetics, Quercetin, Spectrum Analysis, Protein Structure, Secondary, Phyllanthus emblica, Polyphenols, Molecular Docking Simulation

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