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Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models

BACKGROUND: Alzheimer’s disease (AD) is the most common type of presenile and senile dementia. The human β-amyloid precursor cleavage enzyme (BACE-1) is a key enzyme responsible for amyloid plaque production, which implicates the progress and symptoms of AD. Here we assessed the anti-BACE-1 and beha...

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Autores principales: Wang, Xue, Kim, Jun-Ran, Lee, Seong-Baek, Kim, Young-Joon, Jung, Moon Young, Kwon, Hyung-Wook, Ahn, Young-Joon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946151/
https://www.ncbi.nlm.nih.gov/pubmed/24597901
http://dx.doi.org/10.1186/1472-6882-14-88
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author Wang, Xue
Kim, Jun-Ran
Lee, Seong-Baek
Kim, Young-Joon
Jung, Moon Young
Kwon, Hyung-Wook
Ahn, Young-Joon
author_facet Wang, Xue
Kim, Jun-Ran
Lee, Seong-Baek
Kim, Young-Joon
Jung, Moon Young
Kwon, Hyung-Wook
Ahn, Young-Joon
author_sort Wang, Xue
collection PubMed
description BACKGROUND: Alzheimer’s disease (AD) is the most common type of presenile and senile dementia. The human β-amyloid precursor cleavage enzyme (BACE-1) is a key enzyme responsible for amyloid plaque production, which implicates the progress and symptoms of AD. Here we assessed the anti-BACE-1 and behavioral activities of curcuminoids from rhizomes of Curcuma longa (Zingiberaceae), diarylalkyls curcumin (CCN), demethoxycurcumin (DMCCN), and bisdemethoxycurcumin (BDMCCN) against AD Drosophila melanogaster models. METHODS: Neuro-protective ability of the curcuminoids was assessed using Drosophila melanogaster model system overexpressing BACE-1 and its substrate APP in compound eyes and entire neurons. Feeding and climbing activity, lifespan, and morphostructural changes in fly eyes also were evaluated. RESULTS: BDMCCN has the strongest inhibitory activity toward BACE-1 with 17 μM IC(50), which was 20 and 13 times lower than those of CCN and DMCCN respectively. Overexpression of APP/BACE-1 resulted in the progressive and measurable defects in morphology of eyes and locomotion. Remarkably, supplementing diet with either 1 mM BDMCCN or 1 mM CCN rescued APP/BACE1-expressing flies and kept them from developing both morphological and behavioral defects. Our results suggest that structural characteristics, such as degrees of saturation, types of carbon skeleton and functional group, and hydrophobicity appear to play a role in determining inhibitory potency of curcuminoids on BACE-1. CONCLUSION: Further studies will warrant possible applications of curcuminoids as therapeutic BACE-1 blockers.
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spelling pubmed-39461512014-03-09 Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models Wang, Xue Kim, Jun-Ran Lee, Seong-Baek Kim, Young-Joon Jung, Moon Young Kwon, Hyung-Wook Ahn, Young-Joon BMC Complement Altern Med Research Article BACKGROUND: Alzheimer’s disease (AD) is the most common type of presenile and senile dementia. The human β-amyloid precursor cleavage enzyme (BACE-1) is a key enzyme responsible for amyloid plaque production, which implicates the progress and symptoms of AD. Here we assessed the anti-BACE-1 and behavioral activities of curcuminoids from rhizomes of Curcuma longa (Zingiberaceae), diarylalkyls curcumin (CCN), demethoxycurcumin (DMCCN), and bisdemethoxycurcumin (BDMCCN) against AD Drosophila melanogaster models. METHODS: Neuro-protective ability of the curcuminoids was assessed using Drosophila melanogaster model system overexpressing BACE-1 and its substrate APP in compound eyes and entire neurons. Feeding and climbing activity, lifespan, and morphostructural changes in fly eyes also were evaluated. RESULTS: BDMCCN has the strongest inhibitory activity toward BACE-1 with 17 μM IC(50), which was 20 and 13 times lower than those of CCN and DMCCN respectively. Overexpression of APP/BACE-1 resulted in the progressive and measurable defects in morphology of eyes and locomotion. Remarkably, supplementing diet with either 1 mM BDMCCN or 1 mM CCN rescued APP/BACE1-expressing flies and kept them from developing both morphological and behavioral defects. Our results suggest that structural characteristics, such as degrees of saturation, types of carbon skeleton and functional group, and hydrophobicity appear to play a role in determining inhibitory potency of curcuminoids on BACE-1. CONCLUSION: Further studies will warrant possible applications of curcuminoids as therapeutic BACE-1 blockers. BioMed Central 2014-03-05 /pmc/articles/PMC3946151/ /pubmed/24597901 http://dx.doi.org/10.1186/1472-6882-14-88 Text en Copyright © 2014 Wang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Research Article
Wang, Xue
Kim, Jun-Ran
Lee, Seong-Baek
Kim, Young-Joon
Jung, Moon Young
Kwon, Hyung-Wook
Ahn, Young-Joon
Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models
title Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models
title_full Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models
title_fullStr Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models
title_full_unstemmed Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models
title_short Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models
title_sort effects of curcuminoids identified in rhizomes of curcuma longa on bace-1 inhibitory and behavioral activity and lifespan of alzheimer’s disease drosophila models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946151/
https://www.ncbi.nlm.nih.gov/pubmed/24597901
http://dx.doi.org/10.1186/1472-6882-14-88
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