Integration of Network Pharmacology and Molecular Docking Technology
Reveals the Mechanism of the Therapeutic Effect of Xixin Decoction on
Alzheimer's Disease

Zhuo      Zhang; Jianglin      Xu; Suya      Ma; Nan      Lin; Minzhe      Hou; Mingqing      Wei; Ting      Li; Jing      Shi

doi:10.2174/1386207325666220523151119

Abstract

Background: So far, only a few researchers have systematically analyzed the constituents of the traditional Chinese medicine prescription Xixin Decoction (XXD) and its potential mechanism of action in treating Alzheimer’s disease (AD). This study aimed to explore the potential mechanism of XXD in the treatment of AD using network pharmacology and molecular docking.

Methods: The compounds of XXD were searched within the Traditional Chinese Medicine System Pharmacology Database (TCMSP) and the Traditional Chinese Medicine Integrated Database (TCMID) databases. Overlapping AD-related targets obtained from the two databases and the predicted targets of XXD obtained from SwissTargetPrediction platform were imported into the STRING database to build PPI networks including hub targets; Cytoscape software was used to construct the herb-compound-target network while its plug-in CytoNCA was used to screen the main active compounds of XXD. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses explored the core biological mechanism and pathways via the Metascape platform. In addition, we used AutoDock Vina and PyMOL software to investigate the molecular docking of main compounds to hub targets.

Results: We determined 114 active compounds, 973 drug targets, and 973 disease targets. However, intersection analysis screened out 208 shared targets.Protein-protein interaction (PPI) network identified 9 hub targets. The hub targets were found to be majorly enriched in several biological processes (positive regulation of kinase activity, positive regulation of cell death, regulation of MAPK cascade, trans-synaptic signaling, synaptic signaling, etc.) and the relevant pathways of Alzheimer's disease, including neuroactive ligand-receptor interaction, dopaminergic synapse, serotonergic synapse, and the MAPK signaling pathway, etc. The pathway-target-compound network of XXD for treating AD was then constructed. 8 hub targets exhibited good binding activity with 9 main active compounds of XXD in molecular docking.

Conclusion: In this study, we found multi-compound-multi-target-multi-pathway regulation to reveal the mechanism of XXD for treating AD based on network pharmacology and molecular docking. XXD may play a therapeutic role through regulating the Alzheimer's disease pathway, its downstream PI3K/Akt signaling pathway or the MAPK signaling pathway, thereby treating AD. This provides new insights for further experiments on the pharmacological effects of XXD.

Keywords: Xixin decoction, Alzheimer’s disease, network pharmacology, molecular docking, traditional chinese medicine, MAPK signaling pathway.

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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1386207325666220523151119	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402

Combinatorial Chemistry & High Throughput Screening

Integration of Network Pharmacology and Molecular Docking Technology Reveals the Mechanism of the Therapeutic Effect of Xixin Decoction on Alzheimer's Disease

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