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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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