Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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
_version_ 1784668868521754624
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
work_keys_str_mv AT zhangyujia thefoodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT huangqiaoyan thefoodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT wangsichen thefoodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT liaoziqian thefoodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT jinhaichao thefoodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT huangshuo thefoodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT hongxiao thefoodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT liuyiming thefoodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT pangjie thefoodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT shenqing thefoodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT wangqingcheng thefoodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT lichangyu thefoodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT jiliting thefoodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT zhangyujia foodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT huangqiaoyan foodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT wangsichen foodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT liaoziqian foodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT jinhaichao foodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT huangshuo foodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT hongxiao foodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT liuyiming foodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT pangjie foodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT shenqing foodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT wangqingcheng foodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT lichangyu foodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway
AT jiliting foodadditivebcaryophylleneexertsitsneuroprotectiveeffectsthroughthejak2stat3bace1pathway