关键词: 桃红四物汤, 血小板活化, 网络药理学, 分子对接

Abstract: Objective To provide reference for subsequent experimental research and clinical application, the mechanism of Taohongsiwu decoction on platelet activation was explored by network pharmacology and molecular docking technology. Methods First,we obtained the information of the main active ingredients and their corresponding targets in Taohongsiwu decoction from TCMSP database, and the targets related to platelet activation from GeneCard, OMIM, TTD and other databases; secondly, we used the Venny diagram to match the target genes corresponding to the active ingredients in Taohongsiwu decoction to the target genes of platelet activation, and then we screened the common targets between the two. Then, using the STRING platform and Cytoscape 3.7.1 software, we mapped the intersecting gene-protein interactions (PPI) network; then, we used the Gene Annotation, Visualization and Comprehensive Discovery Database (David) database to perform gene ontology (GO) biofunctional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the core targets, and then we used the Microbiology Cloud Platform to analyze the enrichment of the core targets. The enrichment results were visualized on the Microbiology Cloud Platform; finally, molecular docking of the core components and key target genes were carried out with the help of AutoDock Tools software to screen out the important components of Taohongsiwu decoction and their important targets in the process of platelet activation, which provided an important basis for the subsequent experimental validation on the inhibition of platelet activation by the core components. Results A total of 69 active ingredients and 2 175 targets of platelet activation in Taohongsiwu decoction were screened according to certain conditions, and after removing duplicates, 44 active ingredients and 154 key intersecting targets of platelet activation in Taohongsiwu decoction were obtained, and five key targets were finally obtained by using PPI network analysis and related literature, including protein kinase B1 (AKTI),prostaglandin endoperoxide synthase 1 (PTGS1/COX1). collagen type I α1 (COL1A1), collagen type III α1 (COL3A1), and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit γ (PIK3CG/PI3K); the analysis of the GO function and KEGG pathway enrichment showed that the peach red tetrapod soup acted on platelet activated during the platelet activation, Positive regulation of endothelial cell migration, platelet aggregation, platelet α-granule lumen, integrin binding and other biological processes in the process of platelet activation, regulating platelet activation, C-type lectin receptor signaling pathway, PI3K-Akt and other signaling pathways, and thus exerting inhibitory effects on platelet activation. The results of molecular docking showed that there were molecular binding sites between the five main active ingredients of Taohongsiwu decoction and the key targets and the binding energies were strong, all of which were less than -5 kcal /mol. Conclusion This study initially revealed that the mechanism of the inhibition of platelet activation by Taohongsiwu decoction may be realized through the action of multi-targets and multi-pathways.

Key words: Taohongsiwu decoction, Platelet activation, Pharmacology, Molecular docking