基于网络药理学及分子对接技术探讨木槿花–黄芪配伍防治糖尿病心肌病的机制

Exploring Mechanism of the Hibiscus syriacus L.-Astragalus membranaceus Combination against Diabetic Cardiomyopathy Based on Network Pharmacology and Molecular Docking Technology

摘要: 目的：运用网络药理学及分子对接技术探究木槿花–黄芪配伍防治糖尿病心肌病的作用机制。方法：利用HERB和TCMSP数据库分别收集木槿花和黄芪成分，并利用SwissADME平台进一步筛选出活性成分，通过SwissTargetPrediction工具获得活性成分作用的靶点；利用GeneCarfds、OMIM、DrugBank数据库检索DCM作用的靶点，绘制韦恩图展示药物和疾病的交集靶点。利用Cytoscape3.7.0软件构建“中药–成分–疾病–靶点”网络图。利用STRING数据库构建蛋白质互相作用网络(PPI)，并借助Cytoscape3.7.0软件中的Centiscape2.2插件筛选核心靶点。利用Metascape数据库对交集靶点进行GO分析和KEGG富集分析。将Degree排名前6的核心靶点与对应的活性成分通过AutodockTools1.1.2软件进行分子对接验证(共42对)。结果：筛选得到18种有效成分(木槿花4种，黄芪14种)、395个药物作用的靶点和2221个疾病作用的靶点、124个药物与疾病的交集靶点。核心靶点包括表皮生长因子受体(EGFR, degree = 84)、半胱天冬酶3 (CASP3, degree = 80)、雌激素受体α (ESR1, degree = 80)等9个。GO分析筛选出生物学过程、细胞组成、分子功能的前10位，KEGG分析结果富集于PI3K-Akt、ErbB及AGE-RAGE等信号通路。分子对接分析表明木槿花和黄芪的活性成分与治疗DCM的关键靶点结合良好，其中，8'-表黄花菜木脂素A和槲皮素与EGFR结合最为稳定。结论：新型复方中药木槿花–黄芪可以通过多成分、多靶点、多通路防治DCM，8'-表黄花菜木脂素A和槲皮素有望成为治疗DCM药物研发的有效成分，该研究为其临床应用提供科学依据。

Abstract: Objective: To investigate the mechanism of the Hibiscus syriacus L.-Astragalus membranaceus combination against diabetic cardiomyopathy using network pharmacology and molecular docking technology. Methods: Active components of Hibiscus syriacus L. and Astragalus membranaceus were retrieved from the HERB and TCMSP databases, respectively. Drug-likeness screening was performed using the SwissADME platform, and potential targets of active ingredients were predicted via SwissTargetPrediction. Disease-related targets for DCM were obtained from GeneCards, OMIM, and DrugBank. Intersection targets between drug and disease were visualized using Venn diagrams. The “TCM-Ingredient-Disease-Target” network was constructed with Cytoscape 3.7.0. Protein-protein interaction network (PPI) was established using STRING, and core targets were identified via Centiscape 2.2 plugin in Cytoscape 3.7.0 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted using Metascape. Molecular docking validation was performed for the top six core targets and corresponding active ingredients (42 pairs) using AutoDockTools 1.1.2. Results: 18 active ingredients, 395 drug targets, 2221 disease targets, and 124 intersection targets were identified. Nine key targets included EGFR, CASP3, ESR1 and others. GO analysis revealed enriched biological processes, cellular components, and molecular functions. KEGG pathways included PI3K-Akt, ErbB, and AGE-RAGE signaling. Molecular docking demonstrated strong binding affinity between active ingredients (e.g., 8'-epiflora lignan A and quercetin) and core targets, particularly EGFR. Conclusion: The Hibiscus syriacus L.-Astragalus membranaceus combination exerts therapeutic effects on DCM through multi-component, multi-target, and multi-pathway mechanisms. 8'-Epiflora lignan A and quercetin are proposed as potential therapeutic agents, providing a scientific foundation for clinical development.