Combining Serum Pharmacochemistry and Network Pharmacology to Explore the Pharmacodynamic Material Basis and Mechanisms of Yangxinshi Tablet in Treating Coronary Heart Disease

OBJECTIVE To explore the pharmacodynamic material basis and mechanisms of Yangxinshi tablet(YXST) in treating coronary heart disease. METHODS HPLC-ESI-Q-TOF-MS/MS method was performed to analyze the blood-entry components of YXST. The targets of blood-entry compounds were derived from STITCH, TCMSP and Binding DB database. The targets related to coronary heart disease were collected from TTD, DrugBank, PharmGKB, MalaCards and CTD database. Protein-protein interaction(PPI) network was constructed for the obtained compound targets and disease targets using STRING database to screen potential anti-coronary heart disease targets of YXST. Gene ontology(GO) function annotation and kyoto encyclopedia of genes and genomes(KEGG) pathway analysis of potential targets were performed using the clusterProfiler package in R. The blood-entry components-potential target network was further constructed by Cytoscape software to obtain key compounds and key targets. RESULTS Rat plasma after oral administration of YXST was analyzed and 26 prototype compounds could be detected. A total of 287 compound targets corresponding to blood entry components and 199 disease targets associated with coronary heart disease were collected in the database. By intersection analysis and PPI network construction, 70 potential anti-coronary heart disease targets of YXST were obtained. According to the results of GO function annotation and KEGG pathway analysis, YXST treating coronary heart disease mainly involved in the inflammatory response, oxidative stress and advanced glycationend products-receptor for advanced glycationend products(AGE-RAGE), atherosclerosis, tumour necrosis factor(TNF), interleukin-17(IL-17), C-type lectin receptor, Th17 cell differentiation and Toll-like receptor signaling pathways. By constructing and analyzing the blood-entry components-potential target network, 3 key compounds and 16 key targets were obtained. CONCLUSION YXST can interfere with the inflammatory response, oxidative stress and atherosclerosis process by regulating TNF, PTGS2, NOS2 and NOS3. The potential effective compounds are daidzein, berberine and puerarin. This study fully reflect the characteristics of YXST in treating coronary heart disease through multi-component, multi-target and multi-pathway, and provide an important reference for further research on the pharmacological mechanisms of YXST.