Anti-amnesic effects of withaferin A, a steroidal lactone isolated from Withania adpressa, on scopolamine-induced memory impairment in mice

Natural secondary metabolites have long served as sources of drugs against various health disorders, among them neurodegenerative diseases especially Alzheimer’s disease (AD). Withanolides, isolated from Withania species, have shown acetylcholinesterase inhibition activity and their neuroprotective...

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Autores principales:	Widad Ben Bakrim, Laila El Bouzidi, Houria Manouze, Jawhar Hafsa, Mansour Sobeh, Saadia Ba-M'hamed, Khalid Bekkouche, Lamfeddal Kouisni
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Alzheimer's disease Withania adpressa Withaferin A Anticholinesterase activity Anti-amnestic effect Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/4a10d01647ac406cb0a5d286d382844f
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spelling	oai:doaj.org-article:4a10d01647ac406cb0a5d286d382844f2021-11-14T04:31:28ZAnti-amnesic effects of withaferin A, a steroidal lactone isolated from Withania adpressa, on scopolamine-induced memory impairment in mice1878-535210.1016/j.arabjc.2021.103529https://doaj.org/article/4a10d01647ac406cb0a5d286d382844f2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S187853522100544Xhttps://doaj.org/toc/1878-5352Natural secondary metabolites have long served as sources of drugs against various health disorders, among them neurodegenerative diseases especially Alzheimer’s disease (AD). Withanolides, isolated from Withania species, have shown acetylcholinesterase inhibition activity and their neuroprotective effects may be beneficial in the treatment of cholinergic system associated diseases, such as AD. This study was undertaken to highlight the neuroprotective effects of withaferin A (WA), isolated from W. adpressa leaves, using a scopolamine-induced memory impairment model in mice. The in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition potentials of WA were assessed. The learning and memory enhancing activities of WA at different doses (1, 3 and 5 mg/kg) were investigated utilizing Novel Object Recognition (NOR) and Barnes maze (BM). WA substantially inhibited AChE and BuChE enzymes with IC50 values of 45.5 ± 0.14 and 68.2 ± 0.27 µg/mL, respectively. Noteworthy, rotarod results revealed no significant differences between WA and control groups. Also, learning, and spatial memory performance in NOR and BM tests were improved compared to the control groups. Furthermore, the activity of acetylcholinesterase in the brain was significantly inhibited (p < 0.05) by WA at the three tested doses. WA possessed certain affinity in both enzymes with low binding energy compared to the reference drug donepezil in a molecular docking study. This study displays that WA could be used for enhancing learning and memory impairment and appears to be a promising candidate for Alzheimer’s disease treatment.Widad Ben BakrimLaila El BouzidiHouria ManouzeJawhar HafsaMansour SobehSaadia Ba-M'hamedKhalid BekkoucheLamfeddal KouisniElsevierarticleAlzheimer's diseaseWithania adpressaWithaferin AAnticholinesterase activityAnti-amnestic effectChemistryQD1-999ENArabian Journal of Chemistry, Vol 15, Iss 1, Pp 103529- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer's disease Withania adpressa Withaferin A Anticholinesterase activity Anti-amnestic effect Chemistry QD1-999
spellingShingle	Alzheimer's disease Withania adpressa Withaferin A Anticholinesterase activity Anti-amnestic effect Chemistry QD1-999 Widad Ben Bakrim Laila El Bouzidi Houria Manouze Jawhar Hafsa Mansour Sobeh Saadia Ba-M'hamed Khalid Bekkouche Lamfeddal Kouisni Anti-amnesic effects of withaferin A, a steroidal lactone isolated from Withania adpressa, on scopolamine-induced memory impairment in mice
description	Natural secondary metabolites have long served as sources of drugs against various health disorders, among them neurodegenerative diseases especially Alzheimer’s disease (AD). Withanolides, isolated from Withania species, have shown acetylcholinesterase inhibition activity and their neuroprotective effects may be beneficial in the treatment of cholinergic system associated diseases, such as AD. This study was undertaken to highlight the neuroprotective effects of withaferin A (WA), isolated from W. adpressa leaves, using a scopolamine-induced memory impairment model in mice. The in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition potentials of WA were assessed. The learning and memory enhancing activities of WA at different doses (1, 3 and 5 mg/kg) were investigated utilizing Novel Object Recognition (NOR) and Barnes maze (BM). WA substantially inhibited AChE and BuChE enzymes with IC50 values of 45.5 ± 0.14 and 68.2 ± 0.27 µg/mL, respectively. Noteworthy, rotarod results revealed no significant differences between WA and control groups. Also, learning, and spatial memory performance in NOR and BM tests were improved compared to the control groups. Furthermore, the activity of acetylcholinesterase in the brain was significantly inhibited (p < 0.05) by WA at the three tested doses. WA possessed certain affinity in both enzymes with low binding energy compared to the reference drug donepezil in a molecular docking study. This study displays that WA could be used for enhancing learning and memory impairment and appears to be a promising candidate for Alzheimer’s disease treatment.
format	article
author	Widad Ben Bakrim Laila El Bouzidi Houria Manouze Jawhar Hafsa Mansour Sobeh Saadia Ba-M'hamed Khalid Bekkouche Lamfeddal Kouisni
author_facet	Widad Ben Bakrim Laila El Bouzidi Houria Manouze Jawhar Hafsa Mansour Sobeh Saadia Ba-M'hamed Khalid Bekkouche Lamfeddal Kouisni
author_sort	Widad Ben Bakrim
title	Anti-amnesic effects of withaferin A, a steroidal lactone isolated from Withania adpressa, on scopolamine-induced memory impairment in mice
title_short	Anti-amnesic effects of withaferin A, a steroidal lactone isolated from Withania adpressa, on scopolamine-induced memory impairment in mice
title_full	Anti-amnesic effects of withaferin A, a steroidal lactone isolated from Withania adpressa, on scopolamine-induced memory impairment in mice
title_fullStr	Anti-amnesic effects of withaferin A, a steroidal lactone isolated from Withania adpressa, on scopolamine-induced memory impairment in mice
title_full_unstemmed	Anti-amnesic effects of withaferin A, a steroidal lactone isolated from Withania adpressa, on scopolamine-induced memory impairment in mice
title_sort	anti-amnesic effects of withaferin a, a steroidal lactone isolated from withania adpressa, on scopolamine-induced memory impairment in mice
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/4a10d01647ac406cb0a5d286d382844f
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Anti-amnesic effects of withaferin A, a steroidal lactone isolated from Withania adpressa, on scopolamine-induced memory impairment in mice

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