赤芍干预先天性心脏病的药效物质筛选及多靶点调控机制研究

Screening of Bioactive Components in Radix Paeoniae Rubra for Intervention in Congenital Heart Disease and Study on Multi-Target Regulatory Mechanisms

摘要: 目的：基于网络药理学探究赤芍治疗先天性心脏病的活性成分及其作用机制。方法：通过整合TCMSP数据库及文献挖掘筛选赤芍活性成分与靶点，结合GeneCards、OMIM和DisGeNET数据库获取CHD相关靶标。利用Venny 2.1和Cytoscape 3.7.2软件构建“药物–成分–疾病靶点”网络，基于STRING数据库建立蛋白互作网络，并通过DAVID数据库进行GO功能注释与KEGG通路富集分析。结果：共筛选出赤芍14个活性成分，作用于87个CHD相关靶点，其中β-谷甾醇、鞣花酸等核心成分与AKT1、TNF等关键靶点具有显著结合活性。通路富集分析表明，赤芍主要通过调控PI3K-Akt、TNF及MAPK信号通路，介导炎症反应抑制、细胞凋亡调控及血管内皮功能改善。结论：本研究首次系统揭示赤芍通过多成分、多靶点及多通路协同网络治疗CHD的分子机制，为核心成分的临床应用及创新药物研发提供理论依据。

Abstract: Objective: To investigate the active components of Paeoniae Radix Rubra (Paeonia) and their mechanisms of action in treating congenital heart disease (CHD) based on network pharmacology. Methods: Active components of Paeonia and their targets were screened by integrating the TCMSP database and literature mining. CHD-related targets were retrieved from GeneCards, OMIM, and DisGeNET databases. A “drug-component-disease target” network was constructed using Venny 2.1 and Cytoscape 3.7.2. Protein-protein interaction (PPI) networks were established via the STRING database. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. Results: Fourteen active components of Paeonia targeting 87 CHD-related genes were identified. Core components, including β-sitosterol and ellagic acid, exhibited significant binding activity with key targets such as AKT1 and TNF. Pathway enrichment analysis revealed that Paeonia primarily modulates the PI3K-Akt, TNF, and MAPK signaling pathways to mediate inhibition of inflammatory responses, regulation of apoptosis, and improvement of vascular endothelial function. Conclusion: This study systematically elucidates, for the first time, the molecular mechanism by which Paeonia treats CHD through a multi-component, multi-target, and multi-pathway synergistic network, providing a theoretical foundation for the clinical application of core components and the development of innovative therapeutics.