dc.contributor.author |
Thakur, A
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|
dc.contributor.author |
Moyo, P
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|
dc.contributor.author |
Van Der Westhuizen, Carl Johan
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dc.contributor.author |
Yang, HO
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dc.contributor.author |
Maharaj, V
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dc.date.accessioned |
2022-03-13T16:52:40Z |
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dc.date.available |
2022-03-13T16:52:40Z |
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dc.date.issued |
2021-07 |
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dc.identifier.citation |
Thakur, A., Moyo, P., Van Der Westhuizen, C.J., Yang, H. & Maharaj, V. 2021. A novel cardenolide glycoside isolated from Xysmalobium undulatum reduces levels of the Alzheimer's disease-associated ß-Amyloid peptides aß42 in vitro. <i>Pharmaceuticals (Basel), 14(8).</i> http://hdl.handle.net/10204/12317 |
en_ZA |
dc.identifier.issn |
1424-8247 |
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dc.identifier.uri |
DOI: 10.3390/ph14080743
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|
dc.identifier.uri |
http://hdl.handle.net/10204/12317
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|
dc.description.abstract |
Elevated levels of the amylo ß-proteins (Aß), particularly Aß42, are associated with a high risk of Alzheimer's disease (AD). The Aß proteins are produced from cellular processing of the amyloid precursor proteins (APPs). To identify natural products that block the formation of Aß-proteins from APPs, we previously screened a library of plant extracts and identified Xysmalobium undulaum (Apocynaceae) as a potential plant for further research. Here, we provide a report on the isolation and identification of the active principles from the plant species using a bioassay-guided fractionation. Fractions and resulting pure compounds from the purification process of the extract of X. undulatum were screened in vitro against APPs transfected HeLa cell lines. Three compounds, acetylated glycosydated crotoxogenin (1), xysmalogenin-3, ß-d-glucopyranoside (2), and crotoxigenin 3-O-glucopyranoside (3), were subsequently isolated and their structures elucidated using NMR and mass spectrometry. Compound 1, a novel cardenolide, and 2 significantly decreased the Aß42 levels in a dose-dependent manner while compound 3 was inactive. In silico investigations identified the AD's ß-secretase enzyme, BACE1, as a potential target for these compounds with the glycoside moiety being of significance in binding to the enzyme active site. Our study provides the first report of a novel cardenolide and the potential of cardenolides as chemical scaffolds for developing AD treatment drugs. |
en_US |
dc.format |
Fulltext |
en_US |
dc.language.iso |
en |
en_US |
dc.relation.uri |
https://www.mdpi.com/1424-8247/14/ |
en_US |
dc.relation.uri |
https://pubmed.ncbi.nlm.nih.gov/34451840/ |
en_US |
dc.source |
Pharmaceuticals (Basel), 14(8) |
en_US |
dc.subject |
Aß42 reduction |
en_US |
dc.subject |
Acetylated glycosydated crotoxigenin |
en_US |
dc.subject |
Alzheimer's disease |
en_US |
dc.subject |
ß-d-glucopyranoside |
en_US |
dc.subject |
Nuclear magnetic resonance |
en_US |
dc.subject |
NMR |
en_US |
dc.subject |
Xysmalogenin-3 |
en_US |
dc.subject |
Xysmalobium undulatum |
en_US |
dc.title |
A novel cardenolide glycoside isolated from Xysmalobium undulatum reduces levels of the Alzheimer's disease-associated ß-Amyloid peptides aß42 in vitro |
en_US |
dc.type |
Article |
en_US |
dc.description.pages |
14 |
en_US |
dc.description.note |
Copyright: © 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 (https://creativecommons.org/licenses/by/4.0/). |
en_US |
dc.description.cluster |
Chemicals |
en_US |
dc.identifier.apacitation |
Thakur, A., Moyo, P., Van Der Westhuizen, C. J., Yang, H., & Maharaj, V. (2021). A novel cardenolide glycoside isolated from Xysmalobium undulatum reduces levels of the Alzheimer's disease-associated ß-Amyloid peptides aß42 in vitro. <i>Pharmaceuticals (Basel), 14(8)</i>, http://hdl.handle.net/10204/12317 |
en_ZA |
dc.identifier.chicagocitation |
Thakur, A, P Moyo, Carl Johan Van Der Westhuizen, HO Yang, and V Maharaj "A novel cardenolide glycoside isolated from Xysmalobium undulatum reduces levels of the Alzheimer's disease-associated ß-Amyloid peptides aß42 in vitro." <i>Pharmaceuticals (Basel), 14(8)</i> (2021) http://hdl.handle.net/10204/12317 |
en_ZA |
dc.identifier.vancouvercitation |
Thakur A, Moyo P, Van Der Westhuizen CJ, Yang H, Maharaj V. A novel cardenolide glycoside isolated from Xysmalobium undulatum reduces levels of the Alzheimer's disease-associated ß-Amyloid peptides aß42 in vitro. Pharmaceuticals (Basel), 14(8). 2021; http://hdl.handle.net/10204/12317. |
en_ZA |
dc.identifier.ris |
TY - Article
AU - Thakur, A
AU - Moyo, P
AU - Van Der Westhuizen, Carl Johan
AU - Yang, HO
AU - Maharaj, V
AB - Elevated levels of the amylo ß-proteins (Aß), particularly Aß42, are associated with a high risk of Alzheimer's disease (AD). The Aß proteins are produced from cellular processing of the amyloid precursor proteins (APPs). To identify natural products that block the formation of Aß-proteins from APPs, we previously screened a library of plant extracts and identified Xysmalobium undulaum (Apocynaceae) as a potential plant for further research. Here, we provide a report on the isolation and identification of the active principles from the plant species using a bioassay-guided fractionation. Fractions and resulting pure compounds from the purification process of the extract of X. undulatum were screened in vitro against APPs transfected HeLa cell lines. Three compounds, acetylated glycosydated crotoxogenin (1), xysmalogenin-3, ß-d-glucopyranoside (2), and crotoxigenin 3-O-glucopyranoside (3), were subsequently isolated and their structures elucidated using NMR and mass spectrometry. Compound 1, a novel cardenolide, and 2 significantly decreased the Aß42 levels in a dose-dependent manner while compound 3 was inactive. In silico investigations identified the AD's ß-secretase enzyme, BACE1, as a potential target for these compounds with the glycoside moiety being of significance in binding to the enzyme active site. Our study provides the first report of a novel cardenolide and the potential of cardenolides as chemical scaffolds for developing AD treatment drugs.
DA - 2021-07
DB - ResearchSpace
DP - CSIR
J1 - Pharmaceuticals (Basel), 14(8)
KW - Aß42 reduction
KW - Acetylated glycosydated crotoxigenin
KW - Alzheimer's disease
KW - ß-d-glucopyranoside
KW - Nuclear magnetic resonance
KW - NMR
KW - Xysmalogenin-3
KW - Xysmalobium undulatum
LK - https://researchspace.csir.co.za
PY - 2021
SM - 1424-8247
T1 - A novel cardenolide glycoside isolated from Xysmalobium undulatum reduces levels of the Alzheimer's disease-associated ß-Amyloid peptides aß42 in vitro
TI - A novel cardenolide glycoside isolated from Xysmalobium undulatum reduces levels of the Alzheimer's disease-associated ß-Amyloid peptides aß42 in vitro
UR - http://hdl.handle.net/10204/12317
ER -
|
en_ZA |
dc.identifier.worklist |
25438 |
en_US |