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Neuroprotective Studies of Evodiamine in an Okadaic Acid-Induced Neurotoxicity

Background: Alzheimer’s disease (AD) is the most common neurodegenerative disease, and it manifests as progressive memory loss and cognitive decline. However, there are no effective therapies for AD, which is an urgent problem to solve. Evodiamine, one of the main bioactive ingredients of Evodia rut...

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Autores principales: Chou, Ching-Hsuan, Yang, Chia-Ron
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161163/
https://www.ncbi.nlm.nih.gov/pubmed/34069531
http://dx.doi.org/10.3390/ijms22105347
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author Chou, Ching-Hsuan
Yang, Chia-Ron
author_facet Chou, Ching-Hsuan
Yang, Chia-Ron
author_sort Chou, Ching-Hsuan
collection PubMed
description Background: Alzheimer’s disease (AD) is the most common neurodegenerative disease, and it manifests as progressive memory loss and cognitive decline. However, there are no effective therapies for AD, which is an urgent problem to solve. Evodiamine, one of the main bioactive ingredients of Evodia rutaecarpa, has been reported to ameliorate blood–brain barrier (BBB) permeability and improve cognitive impairment in ischemia and AD mouse models. However, whether evodiamine alleviates tauopathy remains unclear. This study aimed to examine whether evodiamine ameliorates tau phosphorylation and cognitive deficits in AD models. Methods: A protein phosphatase 2A inhibitor, okadaic acid (OA), was used to induce tau phosphorylation to mimic AD-like models in neuronal cells. Protein expression and cell apoptosis were detected using Western blotting and flow cytometry, respectively. Spatial memory/cognition was assessed using water maze, passive avoidance tests, and magnetic resonance imaging assay in OA-induced mice models, and brain slices were evaluated further by immunohistochemistry. Results: The results showed that evodiamine significantly reduced the expression of phosphor-tau, and further decreased tau aggregation and neuronal cell death in response to OA treatment. This inhibition was found to be via the inhibition of glycogen synthase kinase 3β, cyclin-dependent kinase 5, and mitogen-activated protein kinase pathways. In vivo results indicated that evodiamine treatment ameliorated learning and memory impairments in mice, whereas Western blotting and immunohistochemical analysis of the mouse brain also confirmed the neuroprotective effects of evodiamine. Conclusions: Evodiamine can decrease the neurotoxicity of tau aggregation and exhibit a neuroprotective effect. Our results demonstrate that evodiamine has a therapeutic potential for AD treatment.
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spelling pubmed-81611632021-05-29 Neuroprotective Studies of Evodiamine in an Okadaic Acid-Induced Neurotoxicity Chou, Ching-Hsuan Yang, Chia-Ron Int J Mol Sci Article Background: Alzheimer’s disease (AD) is the most common neurodegenerative disease, and it manifests as progressive memory loss and cognitive decline. However, there are no effective therapies for AD, which is an urgent problem to solve. Evodiamine, one of the main bioactive ingredients of Evodia rutaecarpa, has been reported to ameliorate blood–brain barrier (BBB) permeability and improve cognitive impairment in ischemia and AD mouse models. However, whether evodiamine alleviates tauopathy remains unclear. This study aimed to examine whether evodiamine ameliorates tau phosphorylation and cognitive deficits in AD models. Methods: A protein phosphatase 2A inhibitor, okadaic acid (OA), was used to induce tau phosphorylation to mimic AD-like models in neuronal cells. Protein expression and cell apoptosis were detected using Western blotting and flow cytometry, respectively. Spatial memory/cognition was assessed using water maze, passive avoidance tests, and magnetic resonance imaging assay in OA-induced mice models, and brain slices were evaluated further by immunohistochemistry. Results: The results showed that evodiamine significantly reduced the expression of phosphor-tau, and further decreased tau aggregation and neuronal cell death in response to OA treatment. This inhibition was found to be via the inhibition of glycogen synthase kinase 3β, cyclin-dependent kinase 5, and mitogen-activated protein kinase pathways. In vivo results indicated that evodiamine treatment ameliorated learning and memory impairments in mice, whereas Western blotting and immunohistochemical analysis of the mouse brain also confirmed the neuroprotective effects of evodiamine. Conclusions: Evodiamine can decrease the neurotoxicity of tau aggregation and exhibit a neuroprotective effect. Our results demonstrate that evodiamine has a therapeutic potential for AD treatment. MDPI 2021-05-19 /pmc/articles/PMC8161163/ /pubmed/34069531 http://dx.doi.org/10.3390/ijms22105347 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Chou, Ching-Hsuan
Yang, Chia-Ron
Neuroprotective Studies of Evodiamine in an Okadaic Acid-Induced Neurotoxicity
title Neuroprotective Studies of Evodiamine in an Okadaic Acid-Induced Neurotoxicity
title_full Neuroprotective Studies of Evodiamine in an Okadaic Acid-Induced Neurotoxicity
title_fullStr Neuroprotective Studies of Evodiamine in an Okadaic Acid-Induced Neurotoxicity
title_full_unstemmed Neuroprotective Studies of Evodiamine in an Okadaic Acid-Induced Neurotoxicity
title_short Neuroprotective Studies of Evodiamine in an Okadaic Acid-Induced Neurotoxicity
title_sort neuroprotective studies of evodiamine in an okadaic acid-induced neurotoxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161163/
https://www.ncbi.nlm.nih.gov/pubmed/34069531
http://dx.doi.org/10.3390/ijms22105347
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AT yangchiaron neuroprotectivestudiesofevodiamineinanokadaicacidinducedneurotoxicity