Abstract
Since 1990, the incidence of stroke has been rising to become the second leading cause of death in the world, posing a huge burden and challenge to society and families. Astragalus membranaceus and Ligusticum chuanxiong (A&L) have been used as traditional Chinese medicine (TCM) prescriptions to treat and prevent the occurrence of ischemic stroke (IS), but their mechanism of action on the disease has not been fully elucidated. The main objective of this study was to reveal the pharmacological mechanism of A&L in the treatment of IS and to perform preliminary validation. The active ingredients of A&L were obtained from the systematic pharmacology platform of traditional Chinese medicine (TCMSP) database, whereas the genes of IS were obtained from 2 major databases, DrugBank and GeneCards. Cytoscape_v3.8.2 was used to construct the TCM-active ingredient and TCM-active ingredient-cross-target-disease relationship maps, and the MCODE plug-in was used to obtain the core genes, whereas the protein-protein interaction maps were obtained from the STRING database. The results of gene ontology and Kyoto encyclopedia of genes and genomes enrichment were obtained using the Hiplot online tool, and the small molecules in the relevant signalling pathways were verified by molecular docking using AutoDock. A&L contained a total of 26 eligible active ingredients, sharing 161 common targets with IS. A total of 58 core genes with 1326 edges were obtained using the MCODE plug-in. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment results showed association with interleukin-17 signaling pathway, lipid and atherosclerosis, tumor necrosis factor signaling pathway, and Toll-like receptor signaling pathway, which mainly mediates the development of inflammatory responses. Furthermore, molecular docking was conducted and most of the components were found to have good binding to the receptors. This study demonstrates that A&L can be used to treat IS by controlling the inflammatory response through multiple targets and multiple pathways, and provides a reference for subsequent trials.