01 June 2020 : Laboratory Research
Anti-Alzheimer’s Disease Molecular Mechanism of Acori Tatarinowii Rhizoma Based on Network Pharmacology
Yujia Zhang1AE, Yangshen Wu1B, Yunbo Fu1D, Luning Lin1B, Yiyou Lin1F, Yehui Zhang1F, Liting Ji1AC, Changyu Li2G*DOI: 10.12659/MSMBR.924203
Med Sci Monit Basic Res 2020; 26:e924203
Abstract
BACKGROUND: Acori Tatarinowii Rhizoma (ATR), a traditional Chinese herbal medicine, is used to treat Alzheimer’s disease (AD), which is a worldwide degenerative brain disease. The aim of this study was to identify the potential mechanism and molecular targets of ATR in AD by using network pharmacology.
MATERIAL AND METHODS: The potential targets of the active ingredients of ATR were predicted by PharmMapper, and the targets of Alzheimer’s disease were searched by DisGeNET. All screened genes were intersected to obtain potential targets for the active ingredients of ATR. The protein–protein interaction network of possible targets was established by STRING, GO Enrichment, and KEGG pathway enrichment analyses using the Annotation of DAVID database. Next, Cytoscape was used to build the “components–targets–pathways” networks. Additionally, a “disease–component–gene-pathways” network was constructed and verified by molecular docking methods. In addition, the active constituents β-asarone and β-caryophyllene were used to detect Aβ₁₋₄₂-mediated SH-SY5Y cells, and mRNA expression levels of APP, Tau, and core target genes were estimated by qRT-PCR.
RESULTS: The results showed that the active components of ATR participate in related biological processes such as cancer, inflammation, cellular metabolism, and metabolic pathways and are closely related to the 13 predictive targets: ESR1, PPARG, AR, CASP3, JAK2, MAPK14, MAP2K1, ABL1, PTPN1, NR3C1, MET, INSR, and PRKACA. The ATR active components of β-caryophyllene significantly reduced the mRNA expression levels of APP, TAU, ESR1, PTPN1, and JAK2.
CONCLUSIONS: The targets and mechanism corresponding to the active ingredients of ATR were investigated systematically, and novel ideas and directions were provided to further study the mechanism of ATR in AD.
Keywords: Alzheimer Disease, Pharmacology, Protein Interaction Maps, Acorus, Molecular Docking Simulation, Plant Extracts
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