Exploring the Potential Mechanism of Zhengan Xifeng Decoction for ischemic stroke based on Network pharmacology and Molecular Docking

Abstract

Backgroud Ischemic stroke (IS) is an acute cerebrovascular incident that threatens public health. Zhengan Xifeng Decoction (ZXD), as a common herbal formula, has been widely applied in clinical practice for IS. The purpose of this study was to investigate the bioactive ingredients and potential pharmacological mechanisms of ZXD for IS based on network pharmacology and molecular docking.Methods Chemical ingredients of ZXD were screened from TCMSP, BATMAN-TCM and the literature. Then, the targets of the chemical ingredients were predicted through STITCH and SwissTargetPrediction databases. IS-related targets were selected from DisGeNET, DrugBank, MalaCards and GeneCards databases. And, the String database and Cytoscape 3.8.2 software were used to construct the protein-protein interaction (PPI) network. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were analyzed in Metascape. At last, Molecular docking was carried out using Open Babel GUI, AutoDock 1.5.6 and Pymol.Results 284 active ingredients involving 2353 putative targets were identified in ZXD, of which 1098 targets were linked to IS. A total of 20 core targets including MAPK3, MAPK1, and AKT1 were identified by analyzing PPI network. The biological process associated with IS were related to response to growth factor, apoptotic signaling pathway, MAPK cascade and neuron death. And KEGG enrichment included that Prolactin signaling pathway, VEGF signaling pathway and ErbB signaling pathway were closely correlated with neurogenesis, neurotransmission, synaptic plasticity vascular growth factor regulation, in IS. Finally, molecular docking revealed that core ingredients of Quercetin, Carvone and Asparamide had well-binding ability to core targets.Conclusion The study suggested that ZXD treated IS by modulating multiple targets and pathways. And, the results demonstrated that the mechanism of ZXD anti-IS may be related to the regulation of neuroprotection and angiogenesis through Prolactin signaling pathway, VEGF signaling pathway and the ErbB signaling pathway.