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Identifying the Mechanisms and Molecular Targets of Yizhiqingxin Formula on Alzheimer’s Disease: Coupling Network Pharmacology with GEO Database

Authors Zhang T, Pan L, Cao Y, Liu N, Wei W, Li H

Received 28 June 2020

Accepted for publication 9 September 2020

Published 15 October 2020 Volume 2020:13 Pages 487—502

DOI https://doi.org/10.2147/PGPM.S269726

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Martin Bluth


Tingting Zhang,1,2,* Linlin Pan,3,* Yu Cao,4 Nanyang Liu,2 Wei Wei,1,2 Hao Li2

1College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, ShanDong Province, People’s Republic of China; 2Department of Geratology, Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing, People’s Republic of China; 3Department of Chinese Medicine Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 4Geriatric Laboratory, Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Hao Li
Department of Geratology, Xiyuan Hospital, China Academy of Chinese Medical Science, Haidian District, Beijing, People’s Republic of China
Tel +86 10 6283 5631
Email xyhplihao1965@126.com

Background: Yizhiqingxin formula (YZQX) is a promising formula for the treatment of Alzheimer’s disease (AD) with significant clinical effects. Here, we coupled a network pharmacology approach with the Gene Expression Omnibus (GEO) database to illustrate comprehensive mechanisms and screen for molecular targets of YZQX for AD treatment.
Methods: First, active ingredients of YZQX were screened for the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database with the absorption, distribution, metabolism, and excretion (ADME) parameters. Subsequently, putative targets of active ingredients were predicted using the DrugBank database. AD-related targets were retrieved by analyzing published microarray data (accession number GSE5281). Protein–protein interaction (PPI) networks of YZQX putative targets and AD-related targets were constructed visually and merged to identify candidate targets for YZQX against AD using Cytoscape 3.7.2 software. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to further clarify the biological functions of the candidate targets. The gene-pathway network was established to filter for key target genes.
Results: Forty-three active ingredients were identified, and 193 putative target genes were predicted. Seven hundred and ten targets related to AD were screened with |log2 FC| > 1 and P < 0.05. Based on the PPI network, 110 target genes of YZQX against AD were identified. Moreover, 32 related pathways including the PI3K-Akt signaling pathway, MAPK signaling pathway, ubiquitin-mediated proteolysis, apoptosis and the NF-kappa B signaling pathway were significantly enriched. In the gene-pathway network, MAPK1, AKT1, TP53, MDM2, EGFR, RELA, SRC, GRB2, CUL1, and MYC targets are putative core genes for YZQX in AD treatment.
Conclusion: YZQX against AD may exert its neuroprotective effect via the PI3K-Akt signaling pathway, MAPK signaling pathway, and ubiquitin-mediated proteolysis. YZQX may be a promising drug that can be used in the treatment of AD.

Keywords: Yizhiqingxin formula, Alzheimer’s disease, network pharmacology, mechanism, molecular target

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