The inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit on acetylcholinesterase : A interaction, kinetic, spectroscopic, and molecular simulation study
Copyright © 2022 Elsevier Ltd. All rights reserved..
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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:158 |
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| Enthalten in: |
Food research international (Ottawa, Ont.) - 158(2022) vom: 15. Aug., Seite 111497 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Min [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.07.2022 Date Revised 12.09.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.foodres.2022.111497 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM34360454X |
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| 100 | 1 | |a Wu, Min |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit on acetylcholinesterase |b A interaction, kinetic, spectroscopic, and molecular simulation study |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 19.07.2022 | ||
| 500 | |a Date Revised 12.09.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier Ltd. All rights reserved. | ||
| 520 | |a 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 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Acetylcholinesterase | |
| 650 | 4 | |a Molecular simulations | |
| 650 | 4 | |a Phyllanthus emblica Linn. | |
| 650 | 4 | |a Polyphenols | |
| 650 | 4 | |a Spectroscopy methods | |
| 650 | 7 | |a Polyphenols |2 NLM | |
| 650 | 7 | |a Gallic Acid |2 NLM | |
| 650 | 7 | |a 632XD903SP |2 NLM | |
| 650 | 7 | |a Quercetin |2 NLM | |
| 650 | 7 | |a 9IKM0I5T1E |2 NLM | |
| 650 | 7 | |a Acetylcholinesterase |2 NLM | |
| 650 | 7 | |a EC 3.1.1.7 |2 NLM | |
| 700 | 1 | |a Liu, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Feiyang |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Jianhang |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Qingying |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shanshan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Junxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Zizhong |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Zhengfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Caixia |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Hong |e verfasserin |4 aut | |
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