Uncovering the Mechanism of Chuanhong Stroke Capsule in the Treatment of Stroke Based on Network Pharmacology and Molecular Docking Technology

Abstract

Background and Objective: Chuanhong Stroke Capsule (CHSC) has good clinical efficacy in the treatment of cerebral ischemic stroke (CIS) patients. This study aimed to investigate the pharmacological mechanisms of CHSC in treating CIS using bioinformatics. Methods: The active compounds of CHSC were screened by searching Traditional Chinese Medicine System Pharmacological Database and Analysis Platform (TCMSP), Swiss absorption, distribution, metabolism, and excretion (ADME), PubMed, and China National Knowledge Infrastructure (CNKI) databases. Besides, the potential targets of active compounds were obtained through TCMSP and Swiss Target Prediction databases. CIS targets were obtained from GeneCards, Online Mendelian Inheritance in Man (OMIM), and Gene Expression Omnibus (GEO) databases. CHSC-CIS intersection targets were identified by matching the two, and prediction and analysis of biological functions and pathways of intersection targets was used the enrichments of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, protein–protein interaction (PPI) network, herb-target, and compound-target network of CHSC-CIS were constructed by Cytoscape3.7.2, and herb-compound-pathway network was drawn with Sankey diagram. Finally, AutoDock was used for molecular docking verification, and identifying the active binding sites in target proteins. Results: A total of 293 putative targets were obtained from 62 active compounds in CHSC. Among them, 209 targets were related to CIS. PPI network showed that the top 16 key targets were RELA, JUN, FOS, MAPK1, AKT1, etc. KEGG pathway enrichment analysis demonstrated that CHSC was enriched in PI3K-Akt, MAPK, and TNF signaling pathways. In addition, GO enrichment analysis showed the significant enrichment of CHSC in the following categories: kinase binding, cellular response to nitrogen compound, etc. Network topology analysis showed that quercetin, luteolin, kaempferol, etc., were the key components in CHSC. Finally, molecular docking studies suggested that the active components in CHSC had a good binding ability with the key targets. Conclusions: Our study demonstrated that CHSC exerted the effect in treating CIS by the characteristics of multi-target and multi-pathway, thereby providing a theoretical basis for further study of the effective components and mechanism of CHSC in the treatment of CIS.