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

Sep 30, 2026

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Taohong Siwu Decoction (THSWD) is linked to therapeutic effects in coronary heart disease (CHD), motivating identification of related key genes and mechanisms. CHD-related genes were intersected with THSWD bioactive-component drug-target genes. Mendelian randomization screened candidate key genes causally associated with CHD, followed by Bayesian colocalization to confirm the key locus. An ingredient-target-pathway network and molecular docking validated interactions, highlighting STAT1 and 6-Hydroxynaringenin.

LanguageEnglish

CategoryHealthcare

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Pages12

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Introduction

Network pharmacology and Mendelian randomization workflow

® Observational Study Key genes of Taohong Siwu decoction in treating coronary heart disease based on network pharmacology and Mendelian randomization Chunbin Wang, PhDa ,b ,* , Xin Li, PhDa ,b , Jian Wang, PhDa ,b | Abstract
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 ofTHSWD 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. | | --- | | Abbreviations: AGE-RAGE = advanced glycation end-products receptor for advanced glycation end-products, BP = biological processes, CC = cell components, CHD = coronary heart disease, CI = confidence interval, DL = drug-likeness, eQTL = expression quantitative trait loci, ERBB2 = Erb-b2 receptor tyrosine kinase 2, FLT1 = Fms-like tyrosine kinase 1, GO = gene ontology, IEU Open GWAS = integrative epidemiology unit open genome-wide association study, IVs = instrumental variables, IVW = inverse variance weighted, JAK = Janus kinase, KEGG = Kyoto encyclopedia of genes and genomes, LPL = lipid metabolism, MAPK = mitogen-activated protein kinase, MF = molecular functions, MPO = myeloperoxidase, MR = Mendelian randomization, NF-κB = nuclear factor kappa B, OB = oral bioavailability, OR = odds ratio, PP = posterior probability, PTPN22 = protein tyrosine phosphatase, non-receptor type 22, ROS = reactive oxygen species, SNPs = single nucleotide polymorphisms, SOD = superoxide dismutase, STAT1 = signal transducer and activator of transcription 1, TCM = traditional Chinese nedicines, THSWD = Taohong Siwu Decoction. | | Keywords: coronary heart disease, key genes, Mendelian randomization, Taohong Siwu decoction | This study was funded by grants from the Sichuan Medical Association S2024054 and the Sichuan Science and Technology Program 2024JDKP0032. The funders had no role in the study design, data collection and analysis, decision to publish, or manuscript preparation. The authors have no conflicts of interest to disclose. The datasets generated during and/or analyzed during the current study are publicly available. Ethical approval was not required for t

FAQs

What is the study’s main goal regarding THSWD in coronary heart disease?

To identify key genes related to THSWD’s treatment of CHD and to explore potential biological mechanisms of those key genes.

How were candidate genes selected in the analysis?

CHD-related genes were obtained from public databases and intersected with THSWD bioactive-component drug-target genes to generate candidate genes.

Which key gene and compound were highlighted by the final integrative analyses?

Bayesian colocalization supported STAT1 as the key gene, and molecular docking indicated a binding interaction between STAT1 and 6-Hydroxynaringenin.

Sep 30, 2026

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