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An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease
Alzheimer’s disease (AD) is the most frequent type of dementia. Acteoside (ACT) is a compound isolated from Cistanche tubulosa, which possesses excellent neuroprotective properties. However, the underlying mechanism of ACT in regulating microglia polarization remains ill-defined. Therefore, a comput...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327963/ https://www.ncbi.nlm.nih.gov/pubmed/34350171 http://dx.doi.org/10.3389/fcell.2021.652310 |
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author | Li, Ying-Qi Chen, Yi Jiang, Si-Qi Shi, Yuan-Yuan Jiang, Xiao-Li Wu, Shan-Shan Zhou, Ping Wang, Hui-Ying Li, Ping Li, Fei |
author_facet | Li, Ying-Qi Chen, Yi Jiang, Si-Qi Shi, Yuan-Yuan Jiang, Xiao-Li Wu, Shan-Shan Zhou, Ping Wang, Hui-Ying Li, Ping Li, Fei |
author_sort | Li, Ying-Qi |
collection | PubMed |
description | Alzheimer’s disease (AD) is the most frequent type of dementia. Acteoside (ACT) is a compound isolated from Cistanche tubulosa, which possesses excellent neuroprotective properties. However, the underlying mechanism of ACT in regulating microglia polarization remains ill-defined. Therefore, a computational network model was established to identify the driving targets of ACT and predict its mechanism by integrating multiple available databases. The AlCl(3)-induced AD model in zebrafish larvae was successfully constituted to demonstrate the therapeutic efficacy of ACT. Subsequently, LPS-induced BV-2 cells uncovered the positive role of ACT in M1/M2 polarization. The NF-κB and AMPK pathways were further confirmed by transcriptomic analysis, metabolomics analysis, molecular biology techniques, and molecular docking. The research provided an infusive mechanism of ACT and revealed the connection between metabolism and microglia polarization from the perspective of mitochondrial function. More importantly, it provided a systematic and comprehensive approach for the discovery of drug targets, including the changes in genes, metabolites, and proteins. |
format | Online Article Text |
id | pubmed-8327963 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83279632021-08-03 An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease Li, Ying-Qi Chen, Yi Jiang, Si-Qi Shi, Yuan-Yuan Jiang, Xiao-Li Wu, Shan-Shan Zhou, Ping Wang, Hui-Ying Li, Ping Li, Fei Front Cell Dev Biol Cell and Developmental Biology Alzheimer’s disease (AD) is the most frequent type of dementia. Acteoside (ACT) is a compound isolated from Cistanche tubulosa, which possesses excellent neuroprotective properties. However, the underlying mechanism of ACT in regulating microglia polarization remains ill-defined. Therefore, a computational network model was established to identify the driving targets of ACT and predict its mechanism by integrating multiple available databases. The AlCl(3)-induced AD model in zebrafish larvae was successfully constituted to demonstrate the therapeutic efficacy of ACT. Subsequently, LPS-induced BV-2 cells uncovered the positive role of ACT in M1/M2 polarization. The NF-κB and AMPK pathways were further confirmed by transcriptomic analysis, metabolomics analysis, molecular biology techniques, and molecular docking. The research provided an infusive mechanism of ACT and revealed the connection between metabolism and microglia polarization from the perspective of mitochondrial function. More importantly, it provided a systematic and comprehensive approach for the discovery of drug targets, including the changes in genes, metabolites, and proteins. Frontiers Media S.A. 2021-07-19 /pmc/articles/PMC8327963/ /pubmed/34350171 http://dx.doi.org/10.3389/fcell.2021.652310 Text en Copyright © 2021 Li, Chen, Jiang, Shi, Jiang, Wu, Zhou, Wang, Li and Li. 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 | Cell and Developmental Biology Li, Ying-Qi Chen, Yi Jiang, Si-Qi Shi, Yuan-Yuan Jiang, Xiao-Li Wu, Shan-Shan Zhou, Ping Wang, Hui-Ying Li, Ping Li, Fei An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease |
title | An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease |
title_full | An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease |
title_fullStr | An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease |
title_full_unstemmed | An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease |
title_short | An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease |
title_sort | inhibitor of nf-κb and an agonist of ampk: network prediction and multi-omics integration to derive signaling pathways for acteoside against alzheimer’s disease |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327963/ https://www.ncbi.nlm.nih.gov/pubmed/34350171 http://dx.doi.org/10.3389/fcell.2021.652310 |
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