Exploring the mechanism of wendan decoction in the treatment of ischemic stroke using bioinformatics and network pharmacology

Abstract

We investigated the pharmacological mechanism of WendanDecoction (WDD) in treating ischemicstroke(IS)using network pharmacology and molecular docking methods.The Gene Expression Omnibusdatabase was searched with“stroke” as akeyword, species as“Homosapiens,” andGeneChip data was usedto identify, screen, and analyze thedifferentially expressed genesof IS.The potential active components and related WDDtarget proteins were screened from the Traditional Chinese medicine systems pharmacology database. Cytoscape (3.8.2) was used to construct the drug-disease-target regulatory network, and Bisogenet and the CytoNCA plug-in were used to construct the protein-protein interaction (PPI). Gene Ontology and the Kyoto Encyclopedia of Genes and Genomesenrichment analyses were performed and AutoDock was used for molecular docking verification.A total of 2497 targets were obtained from 181 active compounds in WDD with8relatedIS targets. PPI network showed thatJUN, NFKBIA, FOS, and CDKN1A have high gene node degree values, withJUN exhibitingthe largest value. This suggestedthat JUN maybe amajor potential target for WDD treatment of IS. Enrichment analysis showed that WDD core targets were involved in the IL-17 and TNF signaling pathway, lipid and atherosclerosis, NF kappa B, toll-like receiver, and nod-like receiver signaling pathways. Network topology analysis showed that the key components of WDDwere luteolin, naringin, ligustrazine, beta sitosterol, quercetin, and stigmasterol; eachplayed a key role and may serve ascore compoundsfor treatingIS. Molecular docking results showed that the active components in WDDbind well with key targets.Our results suggest that various active components of WDD play a therapeutic role in IS by regulating multiple targets such as JUN, NFKBIA, FOS, and CDKN1A in multiple channels such as inflammation, immunity, and lipid metabolism.

Keywords

• Wendan decoction
• Ischemic stroke
• Network pharmacology
• Molecular docking