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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...

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Autores principales: Hwang, Jayeong, Youn, Kumju, Lim, Gyutae, Lee, Jinhyuk, Kim, Dong Hyun, Jun, Mira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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