Mechanism of Shen's Yangxin Tongluo Decoction in Treating In-stent Restenosis after Coronary Intervention Based on the Network Pharmacology

LIU Fang; ZHOU Jingya; LI Peng

doi:10.3639/i.issn.2095-3097.2025.02.049

Abstract：Objective To explore the mechanism of Shen's Yangxin Tongluo Decoction in the treatment of in-stent restenosis(ISR)of coronary arteries through network pharmacology,thus providing a novel treatment for ISR after coronary intervention.Methods Active ingredients of Yangxin Tongluo Decoction and their targets were searched in the Traditional Chinese Medicine Systems Pharmacology(TCMSP)platform,and annotated in Uniprot.Key genes associated with coronary heart disease and ISR were searched in the GeneCards.Causal relationships were identified through Mendelian randomization analysis.Furthermore,a protein-protein interaction(PPI)network was constructed using STRINGdb and ggraph packages in R.Significantly enriched biological terms and signaling pathways were screened by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses.Finally,differentially expressed genes(DEGs)of GSE46560 dataset were analyzed using the Gene Expression Omnibus(GEO)database.Results A total of 185 active ingredients and 263 target genes were identified from Yangxin Tongluo Decoction,among which 16 genes were causally related to coronary heart disease.The PPI network analysis showed that AKT1,SOD1,SPP1,and PPARA were the hub genes.GO and KEGG analyses revealed that hub genes were significantly enriched in the drug metabolism,signal transduction,metabolic pathways,and disease-related pathways.In addition,four genes SPP1,PPARA,SOD1,and AKT1 were jointly associated with coronary heart disease and ISR,while HNF1A and ABCC1 were significantly differentially expressed among ISR patients.Conclusion Shen's Yangxin Tongluo Decoction has therapeutic effects on coronary heart disease and ISR through a multi-component,multi-target,and multi-pathway mechanism.This study provides pharmacological evidence for the rational application of Shen's Yangxin Tongluo Decoction in clinical practice,and offers new directions for future research.