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Bisdemethoxycurcumin inhibits oxidative stress and antagonizes Alzheimer's disease by up‐regulating SIRT1

INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disease. It can lead to progressive cognitive impairment, memory loss, and behavioral alterations. So far, the exact cellular and molecular mechanisms underlying this disorder remain unclear. And there are no effective tr...

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Autores principales: Xu, Yan, Hu, Rong, He, Duanqun, Zhou, Guijuan, Wu, Heng, Xu, Chenlin, He, Bing, Wu, Lin, Wang, Yilin, Chang, Yunqian, Ma, Rundong, Xie, Ming, Xiao, Zijian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375129/
https://www.ncbi.nlm.nih.gov/pubmed/32441492
http://dx.doi.org/10.1002/brb3.1655
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author Xu, Yan
Hu, Rong
He, Duanqun
Zhou, Guijuan
Wu, Heng
Xu, Chenlin
He, Bing
Wu, Lin
Wang, Yilin
Chang, Yunqian
Ma, Rundong
Xie, Ming
Xiao, Zijian
author_facet Xu, Yan
Hu, Rong
He, Duanqun
Zhou, Guijuan
Wu, Heng
Xu, Chenlin
He, Bing
Wu, Lin
Wang, Yilin
Chang, Yunqian
Ma, Rundong
Xie, Ming
Xiao, Zijian
author_sort Xu, Yan
collection PubMed
description INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disease. It can lead to progressive cognitive impairment, memory loss, and behavioral alterations. So far, the exact cellular and molecular mechanisms underlying this disorder remain unclear. And there are no effective treatments to prevent, halt, or reverse AD. In recent years, Chinese traditional medicine has become a new force in the treatment of AD, and the typical representatives of natural herbal ingredients are curcumin and its derivatives. Bisdemethoxycurcumin (BDMC), which is a classical derivative of curcumin, was found to have neuroprotective effects against a cell model of Alzheimer's disease (AD) in our previous studies. This study investigated the intrinsic mechanism of BDMC against AD in animal models. METHODS: In this study, BDMC was injected into the lateral ventricles of normal C57BL/6 mice, APP/PS mice, and APP/PS mice treated with EX527 (the inhibitor of SIRT1). Y maze and Morris water maze were used to test the learning and memory ability of mice. Nissl staining was used to observe the morphological changes of neurons. Immunofluorescence staining was used to detect Aβ deposition in mice. The activities of GSH and SOD were determined to observe the levels of oxidative stress in mice. And Western blot analyses were used to detect content of SIRT1 in mice. RESULTS: In the APP/PS mice, after BDMC intervention, their cognitive function improved, oxidative stress adjusted, the number of neurons increased, Aβ deposition decreased, and the level of SIRT1 expression increased. However, when SIRT1 is inhibited, BDMC on the improvement in the learning and memory ability and the improvement on oxidative stress in APP/PS1 mice were reversed. CONCLUSION: Our findings demonstrated that in the AD mice, BDMC has antagonistic effect on AD. And an intermediate step in the antagonism effect is caused by SIRT1 upregulation, which leading to decreased oxidative stress. Based on these, we concluded that BDMC injection into the lateral ventricle can act against AD by upregulating SIRT1 to antioxidative stress.
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spelling pubmed-73751292020-07-22 Bisdemethoxycurcumin inhibits oxidative stress and antagonizes Alzheimer's disease by up‐regulating SIRT1 Xu, Yan Hu, Rong He, Duanqun Zhou, Guijuan Wu, Heng Xu, Chenlin He, Bing Wu, Lin Wang, Yilin Chang, Yunqian Ma, Rundong Xie, Ming Xiao, Zijian Brain Behav Original Research INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disease. It can lead to progressive cognitive impairment, memory loss, and behavioral alterations. So far, the exact cellular and molecular mechanisms underlying this disorder remain unclear. And there are no effective treatments to prevent, halt, or reverse AD. In recent years, Chinese traditional medicine has become a new force in the treatment of AD, and the typical representatives of natural herbal ingredients are curcumin and its derivatives. Bisdemethoxycurcumin (BDMC), which is a classical derivative of curcumin, was found to have neuroprotective effects against a cell model of Alzheimer's disease (AD) in our previous studies. This study investigated the intrinsic mechanism of BDMC against AD in animal models. METHODS: In this study, BDMC was injected into the lateral ventricles of normal C57BL/6 mice, APP/PS mice, and APP/PS mice treated with EX527 (the inhibitor of SIRT1). Y maze and Morris water maze were used to test the learning and memory ability of mice. Nissl staining was used to observe the morphological changes of neurons. Immunofluorescence staining was used to detect Aβ deposition in mice. The activities of GSH and SOD were determined to observe the levels of oxidative stress in mice. And Western blot analyses were used to detect content of SIRT1 in mice. RESULTS: In the APP/PS mice, after BDMC intervention, their cognitive function improved, oxidative stress adjusted, the number of neurons increased, Aβ deposition decreased, and the level of SIRT1 expression increased. However, when SIRT1 is inhibited, BDMC on the improvement in the learning and memory ability and the improvement on oxidative stress in APP/PS1 mice were reversed. CONCLUSION: Our findings demonstrated that in the AD mice, BDMC has antagonistic effect on AD. And an intermediate step in the antagonism effect is caused by SIRT1 upregulation, which leading to decreased oxidative stress. Based on these, we concluded that BDMC injection into the lateral ventricle can act against AD by upregulating SIRT1 to antioxidative stress. John Wiley and Sons Inc. 2020-05-22 /pmc/articles/PMC7375129/ /pubmed/32441492 http://dx.doi.org/10.1002/brb3.1655 Text en © 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Xu, Yan
Hu, Rong
He, Duanqun
Zhou, Guijuan
Wu, Heng
Xu, Chenlin
He, Bing
Wu, Lin
Wang, Yilin
Chang, Yunqian
Ma, Rundong
Xie, Ming
Xiao, Zijian
Bisdemethoxycurcumin inhibits oxidative stress and antagonizes Alzheimer's disease by up‐regulating SIRT1
title Bisdemethoxycurcumin inhibits oxidative stress and antagonizes Alzheimer's disease by up‐regulating SIRT1
title_full Bisdemethoxycurcumin inhibits oxidative stress and antagonizes Alzheimer's disease by up‐regulating SIRT1
title_fullStr Bisdemethoxycurcumin inhibits oxidative stress and antagonizes Alzheimer's disease by up‐regulating SIRT1
title_full_unstemmed Bisdemethoxycurcumin inhibits oxidative stress and antagonizes Alzheimer's disease by up‐regulating SIRT1
title_short Bisdemethoxycurcumin inhibits oxidative stress and antagonizes Alzheimer's disease by up‐regulating SIRT1
title_sort bisdemethoxycurcumin inhibits oxidative stress and antagonizes alzheimer's disease by up‐regulating sirt1
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375129/
https://www.ncbi.nlm.nih.gov/pubmed/32441492
http://dx.doi.org/10.1002/brb3.1655
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