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Discovery of Natural Inhibitors of Cholinesterases from Hydrangea: In Vitro and In Silico Approaches
Alzheimer’s disease (AD) is a neurodegenerative disease conceptualized as a clinical-biological neurodegenerative construct where amyloid-beta pathophysiology is supposed to play a role. The loss of cognitive functions is mostly characterized by the rapid hydrolysis of acetylcholine by cholinesteras...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830924/ https://www.ncbi.nlm.nih.gov/pubmed/33477276 http://dx.doi.org/10.3390/nu13010254 |
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author | Hwang, Jayeong Youn, Kumju Lim, Gyutae Lee, Jinhyuk Kim, Dong Hyun Jun, Mira |
author_facet | Hwang, Jayeong Youn, Kumju Lim, Gyutae Lee, Jinhyuk Kim, Dong Hyun Jun, Mira |
author_sort | Hwang, Jayeong |
collection | PubMed |
description | Alzheimer’s disease (AD) is a neurodegenerative disease conceptualized as a clinical-biological neurodegenerative construct where amyloid-beta pathophysiology is supposed to play a role. The loss of cognitive functions is mostly characterized by the rapid hydrolysis of acetylcholine by cholinesterases including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Moreover, both enzymes are responsible for non-catalytic actions such as interacting with amyloid β peptide (Aβ) which further leads to promote senile plaque formation. In searching for a natural cholinesterase inhibitor, the present study focused on two isocoumarines from hydrangea, thunberginol C (TC) and hydrangenol 8-O-glucoside pentaacetate (HGP). Hydrangea-derived compounds were demonstrated to act as dual inhibitors of both AChE and BChE. Furthermore, the compounds exerted selective and non-competitive mode of inhibition via hydrophobic interaction with peripheral anionic site (PAS) of the enzymes. Overall results demonstrated that these natural hydrangea-derived compounds acted as selective dual inhibitors of AChE and BChE, which provides the possibility of potential source of new type of anti-cholinesterases with non-competitive binding property with PAS. |
format | Online Article Text |
id | pubmed-7830924 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78309242021-01-26 Discovery of Natural Inhibitors of Cholinesterases from Hydrangea: In Vitro and In Silico Approaches Hwang, Jayeong Youn, Kumju Lim, Gyutae Lee, Jinhyuk Kim, Dong Hyun Jun, Mira Nutrients Article Alzheimer’s disease (AD) is a neurodegenerative disease conceptualized as a clinical-biological neurodegenerative construct where amyloid-beta pathophysiology is supposed to play a role. The loss of cognitive functions is mostly characterized by the rapid hydrolysis of acetylcholine by cholinesterases including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Moreover, both enzymes are responsible for non-catalytic actions such as interacting with amyloid β peptide (Aβ) which further leads to promote senile plaque formation. In searching for a natural cholinesterase inhibitor, the present study focused on two isocoumarines from hydrangea, thunberginol C (TC) and hydrangenol 8-O-glucoside pentaacetate (HGP). Hydrangea-derived compounds were demonstrated to act as dual inhibitors of both AChE and BChE. Furthermore, the compounds exerted selective and non-competitive mode of inhibition via hydrophobic interaction with peripheral anionic site (PAS) of the enzymes. Overall results demonstrated that these natural hydrangea-derived compounds acted as selective dual inhibitors of AChE and BChE, which provides the possibility of potential source of new type of anti-cholinesterases with non-competitive binding property with PAS. MDPI 2021-01-17 /pmc/articles/PMC7830924/ /pubmed/33477276 http://dx.doi.org/10.3390/nu13010254 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hwang, Jayeong Youn, Kumju Lim, Gyutae Lee, Jinhyuk Kim, Dong Hyun Jun, Mira Discovery of Natural Inhibitors of Cholinesterases from Hydrangea: In Vitro and In Silico Approaches |
title | Discovery of Natural Inhibitors of Cholinesterases from Hydrangea: In Vitro and In Silico Approaches |
title_full | Discovery of Natural Inhibitors of Cholinesterases from Hydrangea: In Vitro and In Silico Approaches |
title_fullStr | Discovery of Natural Inhibitors of Cholinesterases from Hydrangea: In Vitro and In Silico Approaches |
title_full_unstemmed | Discovery of Natural Inhibitors of Cholinesterases from Hydrangea: In Vitro and In Silico Approaches |
title_short | Discovery of Natural Inhibitors of Cholinesterases from Hydrangea: In Vitro and In Silico Approaches |
title_sort | discovery of natural inhibitors of cholinesterases from hydrangea: in vitro and in silico approaches |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830924/ https://www.ncbi.nlm.nih.gov/pubmed/33477276 http://dx.doi.org/10.3390/nu13010254 |
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