Acetylcholinesterase and monoamine oxidase-B inhibitory activities by ellagic acid derivatives isolated from Castanopsis cuspidata var. sieboldii

Abstract Among 276 herbal extracts, a methanol extract of Castanopsis cuspidata var. sieboldii stems was selected as an experimental source for novel acetylcholinesterase (AChE) inhibitors. Five compounds were isolated from the extract by activity-guided screening, and their inhibitory activities ag...

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Autores principales:	Jong Min Oh, Hyun-Jae Jang, Myung-Gyun Kang, Soobin Song, Doo-Young Kim, Jung‑Hee Kim, Ji-In Noh, Jong Eun Park, Daeui Park, Sung-Tae Yee, Hoon Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4bf6a6a34e9b438b8713b789b7d987c9
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spelling	oai:doaj.org-article:4bf6a6a34e9b438b8713b789b7d987c92021-12-02T18:34:13ZAcetylcholinesterase and monoamine oxidase-B inhibitory activities by ellagic acid derivatives isolated from Castanopsis cuspidata var. sieboldii10.1038/s41598-021-93458-42045-2322https://doaj.org/article/4bf6a6a34e9b438b8713b789b7d987c92021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93458-4https://doaj.org/toc/2045-2322Abstract Among 276 herbal extracts, a methanol extract of Castanopsis cuspidata var. sieboldii stems was selected as an experimental source for novel acetylcholinesterase (AChE) inhibitors. Five compounds were isolated from the extract by activity-guided screening, and their inhibitory activities against butyrylcholinesterase (BChE), monoamine oxidases (MAOs), and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) were also evaluated. Of these compounds, 4′-O-(α-l-rhamnopyranosyl)-3,3′,4-tri-O-methylellagic acid (3) and 3,3′,4-tri-O-methylellagic acid (4) effectively inhibited AChE with IC50 values of 10.1 and 10.7 µM, respectively. Ellagic acid (5) inhibited AChE (IC50 = 41.7 µM) less than 3 and 4. In addition, 3 effectively inhibited MAO-B (IC50 = 7.27 µM) followed by 5 (IC50 = 9.21 µM). All five compounds weakly inhibited BChE and BACE-1. Compounds 3, 4, and 5 reversibly and competitively inhibited AChE, and were slightly or non-toxic to MDCK cells. The binding energies of 3 and 4 (− 8.5 and − 9.2 kcal/mol, respectively) for AChE were greater than that of 5 (− 8.3 kcal/mol), and 3 and 4 formed a hydrogen bond with Tyr124 in AChE. These results suggest 3 is a dual-targeting inhibitor of AChE and MAO-B, and that these compounds should be viewed as potential therapeutics for the treatment of Alzheimer’s disease.Jong Min OhHyun-Jae JangMyung-Gyun KangSoobin SongDoo-Young KimJung‑Hee KimJi-In NohJong Eun ParkDaeui ParkSung-Tae YeeHoon KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jong Min Oh Hyun-Jae Jang Myung-Gyun Kang Soobin Song Doo-Young Kim Jung‑Hee Kim Ji-In Noh Jong Eun Park Daeui Park Sung-Tae Yee Hoon Kim Acetylcholinesterase and monoamine oxidase-B inhibitory activities by ellagic acid derivatives isolated from Castanopsis cuspidata var. sieboldii
description	Abstract Among 276 herbal extracts, a methanol extract of Castanopsis cuspidata var. sieboldii stems was selected as an experimental source for novel acetylcholinesterase (AChE) inhibitors. Five compounds were isolated from the extract by activity-guided screening, and their inhibitory activities against butyrylcholinesterase (BChE), monoamine oxidases (MAOs), and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) were also evaluated. Of these compounds, 4′-O-(α-l-rhamnopyranosyl)-3,3′,4-tri-O-methylellagic acid (3) and 3,3′,4-tri-O-methylellagic acid (4) effectively inhibited AChE with IC50 values of 10.1 and 10.7 µM, respectively. Ellagic acid (5) inhibited AChE (IC50 = 41.7 µM) less than 3 and 4. In addition, 3 effectively inhibited MAO-B (IC50 = 7.27 µM) followed by 5 (IC50 = 9.21 µM). All five compounds weakly inhibited BChE and BACE-1. Compounds 3, 4, and 5 reversibly and competitively inhibited AChE, and were slightly or non-toxic to MDCK cells. The binding energies of 3 and 4 (− 8.5 and − 9.2 kcal/mol, respectively) for AChE were greater than that of 5 (− 8.3 kcal/mol), and 3 and 4 formed a hydrogen bond with Tyr124 in AChE. These results suggest 3 is a dual-targeting inhibitor of AChE and MAO-B, and that these compounds should be viewed as potential therapeutics for the treatment of Alzheimer’s disease.
format	article
author	Jong Min Oh Hyun-Jae Jang Myung-Gyun Kang Soobin Song Doo-Young Kim Jung‑Hee Kim Ji-In Noh Jong Eun Park Daeui Park Sung-Tae Yee Hoon Kim
author_facet	Jong Min Oh Hyun-Jae Jang Myung-Gyun Kang Soobin Song Doo-Young Kim Jung‑Hee Kim Ji-In Noh Jong Eun Park Daeui Park Sung-Tae Yee Hoon Kim
author_sort	Jong Min Oh
title	Acetylcholinesterase and monoamine oxidase-B inhibitory activities by ellagic acid derivatives isolated from Castanopsis cuspidata var. sieboldii
title_short	Acetylcholinesterase and monoamine oxidase-B inhibitory activities by ellagic acid derivatives isolated from Castanopsis cuspidata var. sieboldii
title_full	Acetylcholinesterase and monoamine oxidase-B inhibitory activities by ellagic acid derivatives isolated from Castanopsis cuspidata var. sieboldii
title_fullStr	Acetylcholinesterase and monoamine oxidase-B inhibitory activities by ellagic acid derivatives isolated from Castanopsis cuspidata var. sieboldii
title_full_unstemmed	Acetylcholinesterase and monoamine oxidase-B inhibitory activities by ellagic acid derivatives isolated from Castanopsis cuspidata var. sieboldii
title_sort	acetylcholinesterase and monoamine oxidase-b inhibitory activities by ellagic acid derivatives isolated from castanopsis cuspidata var. sieboldii
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4bf6a6a34e9b438b8713b789b7d987c9
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Acetylcholinesterase and monoamine oxidase-B inhibitory activities by ellagic acid derivatives isolated from Castanopsis cuspidata var. sieboldii

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