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 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.652310

DOI=10.3389/fcell.2021.652310

ISSN=2296-634X

ABSTRACT=Alzheimer's disease (AD) is the most frequent type of dementia. While acteoside (ACT), a compound isolated from Cistanche tubulosa, possesses neuroprotective properties. However, the underlying mechanism in regulating microglia polarization remains ill-defined. A computational network model was established to identify the driving targets of ACT and predict its mechanisms by integrating multiple available databases. AlCl3-induced AD model in zebrafish larvae demonstrated the therapeutic efficacy of ACT. Subsequently, LPS-induced BV-2 cells uncovered the positive role of ACT in M1/M2 polarization. Finally, NF-κB and AMPK pathways were confirmed by transcriptomic analysis, metabolomics analysis, molecular biology techniques and molecular docking. The research provided an infusive mechanism of ACT and illustrated a new perspective based on mitochondrial dysfunction to reveal the connection between metabolism and microglia polarization. More importantly, it provided a systematic and comprehensive approach of drug target discovery, including the changes in genes, metabolites, and proteins.