Network pharmacology and molecular docking-based analysis of protective mechanism of MLIF in ischemic stroke

• DOI: 10.3389/fcvm.2022.1071533
• Publication Date: 2022-11-18T05:43:05Z
• Authors: Mengting Lv; Qiuzhen Zhu; Xinyu Li; Shanshan Deng; Yuchen Guo; Junqing Mao; Yuefan Zhang
• Keywords: KEGG; Candidate gene

This study aimed to evaluate the potential mechanism by which Monocyte locomotion inhibitory factor (MLIF) improves outcome of ischemic stroke (IS) inflammatory injury.Potential MLIF-related targets were predicted using Swiss TargetPrediction and PharmMapper, while IS-related found from GeneCards, PharmGKB, Therapeutic Target Database (TTD). After obtaining intersection these two datasets, Search Tool for Retrieval Interacting Genes/Protein (STRING11.0) database was used analyze protein-protein interaction (PPI) network candidate genes MLIF treatment IS. The imported into Metascape Gene Ontology (GO) functional analysis Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment. top 20 core "MLIF-target-pathway" mapped Cytoscape3.9.1. Using AutoDock Vina1.1.2, molecular docking validation hub carried out. In experimental part, transient middle cerebral artery occlusion (tMCAO) oxygen glucose deprivation (OGD) models protective efficacy expression cytokines putative targets.MLIF expected have an effect on 370 targets. When intersected with 1,289 stroke, 119 therapeutic found. key enriched pathways PI3K-Akt signaling MAPK pathway, etc. GO yielded 1,677 entries (P < 0.01), such as hormone stimulation, response, included AKT1, EGFR, IGF1, MAPK1, MAPK10, MAPK14, result demonstrated that had strong binding capability JNK (MAPK10). in vitro vivo studies also confirmed protected against IS lowering (MAPK10) AP-1 levels decreasing pro-inflammatory (IL-1, IL-6).MLIF may exert a inhibiting response through suppressing JNK/AP-1 pathway.