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The Food Additive β-Caryophyllene Exerts Its Neuroprotective Effects Through the JAK2-STAT3-BACE1 Pathway
Despite extensive research on Alzheimer’s disease (AD), its diagnosis and treatment remain challenging, and no effective therapies are currently available. Amyloid β (Aβ) extracellular plaques and intracellular neurofibrillary tangles are the histological characteristics of AD that have been directl...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919047/ https://www.ncbi.nlm.nih.gov/pubmed/35296033 http://dx.doi.org/10.3389/fnagi.2022.814432 |
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author | Zhang, Yujia Huang, Qiaoyan Wang, Sichen Liao, Ziqian Jin, Haichao Huang, Shuo Hong, Xiao Liu, Yiming Pang, Jie Shen, Qing Wang, Qingcheng Li, Changyu Ji, Liting |
author_facet | Zhang, Yujia Huang, Qiaoyan Wang, Sichen Liao, Ziqian Jin, Haichao Huang, Shuo Hong, Xiao Liu, Yiming Pang, Jie Shen, Qing Wang, Qingcheng Li, Changyu Ji, Liting |
author_sort | Zhang, Yujia |
collection | PubMed |
description | Despite extensive research on Alzheimer’s disease (AD), its diagnosis and treatment remain challenging, and no effective therapies are currently available. Amyloid β (Aβ) extracellular plaques and intracellular neurofibrillary tangles are the histological characteristics of AD that have been directly linked to neuropathological events such as synaptic and neuronal cell loss. In this study, we explored whether the “JAK2-STAT3-BACE1” pathway is involved in neuroprotection conferred by the food flavouring agent β-caryophyllene (BCP). PC-12 cells with overexpressed amyloid-β protein precursor (APP) were utilised to construct an AD model in vitro, which was then split into four groups, namely control, empty vector, APP overexpression, and BCP (5, 10, and 20 μM). CCK-8 was used to evaluate cell viability, immunofluorescence was utilised to examine synaptic morphology, and quantitative real-time polymerase chain reaction and western blot were used to examine gene and protein expression levels. The relative expression levels of JAK2, STAT3, and BACE1 mRNA in the transfected PC-12 cells were found to be significantly upregulated. The cell morphology altered dramatically 72 h after transfection, becoming rounder, with a decrease in cell number. BCP exhibited the potential to dramatically increase PC-12 cell viability while protecting cell morphology. BCP inhibited APP, JAK2, STAT3, BACE1 mRNA and BACE1 protein overexpression, as well as JAK2 and STAT3 hyperphosphorylation. Molecular docking simulated the docking of BCP with JAK2, STAT3, BACE1, CB2. And JAK2 was found to be the most stable protein. In conclusion, inhibition of the “JAK2-STAT3-BACE1” signalling pathway may be one of the mechanisms through which BCP protects neurons and antagonises Aβ’s neurotoxicity. |
format | Online Article Text |
id | pubmed-8919047 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89190472022-03-15 The Food Additive β-Caryophyllene Exerts Its Neuroprotective Effects Through the JAK2-STAT3-BACE1 Pathway Zhang, Yujia Huang, Qiaoyan Wang, Sichen Liao, Ziqian Jin, Haichao Huang, Shuo Hong, Xiao Liu, Yiming Pang, Jie Shen, Qing Wang, Qingcheng Li, Changyu Ji, Liting Front Aging Neurosci Neuroscience Despite extensive research on Alzheimer’s disease (AD), its diagnosis and treatment remain challenging, and no effective therapies are currently available. Amyloid β (Aβ) extracellular plaques and intracellular neurofibrillary tangles are the histological characteristics of AD that have been directly linked to neuropathological events such as synaptic and neuronal cell loss. In this study, we explored whether the “JAK2-STAT3-BACE1” pathway is involved in neuroprotection conferred by the food flavouring agent β-caryophyllene (BCP). PC-12 cells with overexpressed amyloid-β protein precursor (APP) were utilised to construct an AD model in vitro, which was then split into four groups, namely control, empty vector, APP overexpression, and BCP (5, 10, and 20 μM). CCK-8 was used to evaluate cell viability, immunofluorescence was utilised to examine synaptic morphology, and quantitative real-time polymerase chain reaction and western blot were used to examine gene and protein expression levels. The relative expression levels of JAK2, STAT3, and BACE1 mRNA in the transfected PC-12 cells were found to be significantly upregulated. The cell morphology altered dramatically 72 h after transfection, becoming rounder, with a decrease in cell number. BCP exhibited the potential to dramatically increase PC-12 cell viability while protecting cell morphology. BCP inhibited APP, JAK2, STAT3, BACE1 mRNA and BACE1 protein overexpression, as well as JAK2 and STAT3 hyperphosphorylation. Molecular docking simulated the docking of BCP with JAK2, STAT3, BACE1, CB2. And JAK2 was found to be the most stable protein. In conclusion, inhibition of the “JAK2-STAT3-BACE1” signalling pathway may be one of the mechanisms through which BCP protects neurons and antagonises Aβ’s neurotoxicity. Frontiers Media S.A. 2022-02-28 /pmc/articles/PMC8919047/ /pubmed/35296033 http://dx.doi.org/10.3389/fnagi.2022.814432 Text en Copyright © 2022 Zhang, Huang, Wang, Liao, Jin, Huang, Hong, Liu, Pang, Shen, Wang, Li and Ji. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Zhang, Yujia Huang, Qiaoyan Wang, Sichen Liao, Ziqian Jin, Haichao Huang, Shuo Hong, Xiao Liu, Yiming Pang, Jie Shen, Qing Wang, Qingcheng Li, Changyu Ji, Liting The Food Additive β-Caryophyllene Exerts Its Neuroprotective Effects Through the JAK2-STAT3-BACE1 Pathway |
title | The Food Additive β-Caryophyllene Exerts Its Neuroprotective Effects Through the JAK2-STAT3-BACE1 Pathway |
title_full | The Food Additive β-Caryophyllene Exerts Its Neuroprotective Effects Through the JAK2-STAT3-BACE1 Pathway |
title_fullStr | The Food Additive β-Caryophyllene Exerts Its Neuroprotective Effects Through the JAK2-STAT3-BACE1 Pathway |
title_full_unstemmed | The Food Additive β-Caryophyllene Exerts Its Neuroprotective Effects Through the JAK2-STAT3-BACE1 Pathway |
title_short | The Food Additive β-Caryophyllene Exerts Its Neuroprotective Effects Through the JAK2-STAT3-BACE1 Pathway |
title_sort | food additive β-caryophyllene exerts its neuroprotective effects through the jak2-stat3-bace1 pathway |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919047/ https://www.ncbi.nlm.nih.gov/pubmed/35296033 http://dx.doi.org/10.3389/fnagi.2022.814432 |
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