Key genes of Taohong Siwu decoction in treating coronary heart disease based on network pharmacology and Mendelian randomization.

It has been found in previous studies that Taohong Siwu Decoction (THSWD) has therapeutic effects on coronary heart disease (CHD). The aim of this study was to identify the related key genes of THSWD for the treatment of CHD and to examine the potential biological mechanisms of the key genes in CHD. The CHD-related genes (CHDRGs) were obtained from public databases, along with the bioactive components of THSWD and their corresponding drug-target genes. Candidate genes were identified by obtaining the intersection of CHDRGs and drug-target genes. Subsequently, Mendelian randomization analysis was utilized to determine the candidate key genes causally associated with CHD. The final key genes for CHD were obtained through Bayesian colocalization analysis. Following that, an active ingredient-target-pathway network was constructed based on the key genes to explore the interactions. Finally, molecular docking was conducted to verify the binding ability among the key genes and the bioactive components of the drug. In this study, a sum of 117 candidate genes was obtained by intersecting 547 CHDRGs with 880 drug-target genes. Subsequently, Mendelian randomization analysis was conducted to screen out 5 hazardous exposure factors as candidate key genes, namely ERBB2, PTPN22, FLT1, MPO, and signal transducer and activator of transcription 1 (STAT1). Bayesian analysis was then carried out, which determined that only the key gene STAT1 had a colocalization -positive locus with CHD, and STAT1 influenced CHD through this locus. Subsequently, a regulatory network was formed by 26 kyoto encyclopedia of genes and genomes pathways, 57 targets enriched by STAT1, and 51 active ingredients. Among them, the key gene STAT1 had a binding capacity of -7.0 kcal/mol with the active ingredient 6-Hydroxynaringenin. This study provides a scientific basis for the development of THSWD therapy for CHD by identifying a novel target (STAT1) and a compound (6-Hydroxynaringenin). These discoveries might offer novel objectives for diagnosis and treatment strategies of CHD.