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Neuroprotective effect of β-asarone against Alzheimer’s disease: regulation of synaptic plasticity by increased expression of SYP and GluR1

AIM: β-asarone, an active component of Acori graminei rhizome, has been reported to have neuroprotective effects in Alzheimer’s disease. As the underlying mechanism is not known, we investigated the neuroprotective effects of β-asarone in an APP/PS1 double transgenic mouse model and in NG108 cells....

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Autores principales: Liu, Si-jun, Yang, Cong, Zhang, Yue, Su, Ru-yu, Chen, Jun-li, Jiao, Meng-meng, Chen, Hui-fang, Zheng, Na, Luo, Si, Chen, Yun-bo, Quan, Shi-jian, Wang, Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841421/
https://www.ncbi.nlm.nih.gov/pubmed/27143853
http://dx.doi.org/10.2147/DDDT.S93559
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author Liu, Si-jun
Yang, Cong
Zhang, Yue
Su, Ru-yu
Chen, Jun-li
Jiao, Meng-meng
Chen, Hui-fang
Zheng, Na
Luo, Si
Chen, Yun-bo
Quan, Shi-jian
Wang, Qi
author_facet Liu, Si-jun
Yang, Cong
Zhang, Yue
Su, Ru-yu
Chen, Jun-li
Jiao, Meng-meng
Chen, Hui-fang
Zheng, Na
Luo, Si
Chen, Yun-bo
Quan, Shi-jian
Wang, Qi
author_sort Liu, Si-jun
collection PubMed
description AIM: β-asarone, an active component of Acori graminei rhizome, has been reported to have neuroprotective effects in Alzheimer’s disease. As the underlying mechanism is not known, we investigated the neuroprotective effects of β-asarone in an APP/PS1 double transgenic mouse model and in NG108 cells. MATERIALS AND METHODS: APPswe/PS1dE9 double transgenic male mice were randomly assigned to a model group, β-asarone treatment groups (21.2, 42.4, or 84.8 mg/kg/d), or donepezil treatment group (2 mg/kg/d). Donepezil treatment was a positive control, and background- and age-matched wild-type B6 mice were an external control group. β-asarone (95.6% purity) was dissolved in 0.8% Tween 80 and administered by gavage once daily for 2.5 months. Control and model animals received an equal volume of vehicle. After 2.5 months of treatment, behavior of all animals was evaluated in a Morris water maze. Expression of synaptophysin (SYP) and glutamatergic receptor 1 (G1uR1) in the hippocampus and cortex of the double transgenic mice was assayed by Western blotting. The antagonistic effects of β-asarone against amyloid-β peptide (Aβ) were investigated in vitro in the NG108-15 cell line. After 24 hours of incubation, cells were treated with 10 μm Aβ with or without β-asarone at different concentrations (6.25, 12.5, or 25 μM) for an additional 36 hours. The cytotoxicity of β-asarone was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay of cell viability, and cell morphology was evaluated by bright-field microscopy after 24 hours of treatment. The expression of SYP and GluR1 in cells was detected by Western blot assay in the hippocampus and brain cortex tissues of mice. RESULTS: β-asarone at a high dose reduced escape latency and upregulated SYP and GluR1 expression at both medium and high doses. Cell morphology evaluation showed that β-asarone treatment did not result in obvious cell surface spots and cytoplasmic granularity. β-asarone had a dose-dependent effect on cell proliferation. CONCLUSION: β-asarone antagonized the Aβ neurotoxicity in vivo, improved the learning and memory ability of APP/PS1 mice, and increased the expression of SYP and GluR1 both in vivo and in vitro. Thus, β-asarone may be a potential drug for the treatment of Alzheimer’s disease.
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spelling pubmed-48414212016-05-03 Neuroprotective effect of β-asarone against Alzheimer’s disease: regulation of synaptic plasticity by increased expression of SYP and GluR1 Liu, Si-jun Yang, Cong Zhang, Yue Su, Ru-yu Chen, Jun-li Jiao, Meng-meng Chen, Hui-fang Zheng, Na Luo, Si Chen, Yun-bo Quan, Shi-jian Wang, Qi Drug Des Devel Ther Original Research AIM: β-asarone, an active component of Acori graminei rhizome, has been reported to have neuroprotective effects in Alzheimer’s disease. As the underlying mechanism is not known, we investigated the neuroprotective effects of β-asarone in an APP/PS1 double transgenic mouse model and in NG108 cells. MATERIALS AND METHODS: APPswe/PS1dE9 double transgenic male mice were randomly assigned to a model group, β-asarone treatment groups (21.2, 42.4, or 84.8 mg/kg/d), or donepezil treatment group (2 mg/kg/d). Donepezil treatment was a positive control, and background- and age-matched wild-type B6 mice were an external control group. β-asarone (95.6% purity) was dissolved in 0.8% Tween 80 and administered by gavage once daily for 2.5 months. Control and model animals received an equal volume of vehicle. After 2.5 months of treatment, behavior of all animals was evaluated in a Morris water maze. Expression of synaptophysin (SYP) and glutamatergic receptor 1 (G1uR1) in the hippocampus and cortex of the double transgenic mice was assayed by Western blotting. The antagonistic effects of β-asarone against amyloid-β peptide (Aβ) were investigated in vitro in the NG108-15 cell line. After 24 hours of incubation, cells were treated with 10 μm Aβ with or without β-asarone at different concentrations (6.25, 12.5, or 25 μM) for an additional 36 hours. The cytotoxicity of β-asarone was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay of cell viability, and cell morphology was evaluated by bright-field microscopy after 24 hours of treatment. The expression of SYP and GluR1 in cells was detected by Western blot assay in the hippocampus and brain cortex tissues of mice. RESULTS: β-asarone at a high dose reduced escape latency and upregulated SYP and GluR1 expression at both medium and high doses. Cell morphology evaluation showed that β-asarone treatment did not result in obvious cell surface spots and cytoplasmic granularity. β-asarone had a dose-dependent effect on cell proliferation. CONCLUSION: β-asarone antagonized the Aβ neurotoxicity in vivo, improved the learning and memory ability of APP/PS1 mice, and increased the expression of SYP and GluR1 both in vivo and in vitro. Thus, β-asarone may be a potential drug for the treatment of Alzheimer’s disease. Dove Medical Press 2016-04-15 /pmc/articles/PMC4841421/ /pubmed/27143853 http://dx.doi.org/10.2147/DDDT.S93559 Text en © 2016 Liu et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Liu, Si-jun
Yang, Cong
Zhang, Yue
Su, Ru-yu
Chen, Jun-li
Jiao, Meng-meng
Chen, Hui-fang
Zheng, Na
Luo, Si
Chen, Yun-bo
Quan, Shi-jian
Wang, Qi
Neuroprotective effect of β-asarone against Alzheimer’s disease: regulation of synaptic plasticity by increased expression of SYP and GluR1
title Neuroprotective effect of β-asarone against Alzheimer’s disease: regulation of synaptic plasticity by increased expression of SYP and GluR1
title_full Neuroprotective effect of β-asarone against Alzheimer’s disease: regulation of synaptic plasticity by increased expression of SYP and GluR1
title_fullStr Neuroprotective effect of β-asarone against Alzheimer’s disease: regulation of synaptic plasticity by increased expression of SYP and GluR1
title_full_unstemmed Neuroprotective effect of β-asarone against Alzheimer’s disease: regulation of synaptic plasticity by increased expression of SYP and GluR1
title_short Neuroprotective effect of β-asarone against Alzheimer’s disease: regulation of synaptic plasticity by increased expression of SYP and GluR1
title_sort neuroprotective effect of β-asarone against alzheimer’s disease: regulation of synaptic plasticity by increased expression of syp and glur1
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841421/
https://www.ncbi.nlm.nih.gov/pubmed/27143853
http://dx.doi.org/10.2147/DDDT.S93559
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