A network pharmacology approach to explore the mechanism of action of Shengqi Fuzheng Injection in treating ischemic stroke
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE(2020)
Abstract
Objective: To investigate the potential active ingredients in Shengqi Fuzheng Injection (SFI) and the drug's potential mechanism of action in the treatment of ischemic stroke (IS) based on network pharmacology. The active ingredients of SFI and the associated genes were obtained by retrieving the database of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Methods: The IS-associated targets were identified as the intersection of differentially expressed genes (DEG) from GSE122709 and GSE140275 profiles. The intersection of SFI- and IS-associated genes were used as the potential targets. The protein-protein interaction (PPI) network among 24 potential targets was constructed using the STRING database. The functional annotation was performed to obtain the pathways of potential targets using the Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis which enriches the function of genes. GO semantic similarity was employed to identify the targeted hub genes of SFI related to the treatment of IS. To unravel the regulation among the potential targets, the transcription factor-targets-pathway network was identified using the Transcription Regulatory Relationships Unraveled Sentence-based Text (TRRUST). Results: There were 28 active compounds identified in SFI. Among them, 24 potential targets of SFI which were related to the treatment of ischemic stroke and involved in various functions and pathways were explored. Analysis of PPI and transcription factor target prediction indicated that JUN, NOS3 and PTGS2 were the key genes responsible for the treatment ischemic stroke. These genes were simultaneously enriched in the oxytocin signaling pathway. Twelve compounds were predicted to target JUN, NOS3 and PTGS2, while formononetin was the only compound associated with all the hub genes. Conclusion: SFI protects nervous system probably via the the regulation of JUN, NOS3 and PTGS2 in the oxytocin signaling pathway by formononetin. Further biological and clinical studies are warranted to validate the above findings.
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Key words
SFI,ischemic stroke,network pharmacology,transcription factor,formononetin
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