基于网络药理学和分子对接技术分析黄精治疗心力衰竭的药效物质及作用机制

Analysis of Pharmacodynamic Substances and Mechanism of Action of Polygonati Rhizoma in Treating Heart Failure Based on Network Pharmacology and Molecular Docking Technology

摘要:

目的：应用网络药理学和分子对接技术分析黄精治疗心力衰竭（HF） 的药效物质及作用机制。方法：从中药系统药理学数据库与分析平台查找黄精的潜在活性成分及对应靶点，通过GeneCards和OMIM数据库获取HF相关靶点。将黄精潜在成分靶点与HF相关靶点取交集得到黄精治疗HF的潜在作用靶点。利用STRING数据库构建蛋白质相互作用（PPI） 网络并筛选核心靶点和主要活性成分。使用DAVID数据库对交集靶点进行基因本体（GO） 功能和京都基因与基因组百科全书（KEGG） 通路富集分析。最后使用AutoDockTools 软件进行分子对接，评估主要活性成分与核心靶点结合活性。结果：筛选得到黄精活性成分15 个，黄精治疗HF潜在靶点87个。通过“药物-活性成分-靶点”网络分析得到芹菜素、β-谷甾醇、黄芩素、异甘草素、薯蓣皂苷等主要活性成分。通过PPI网络分析得到蛋白激酶B1 （AKT1）、肿瘤坏死因子（TNF）、胰岛素（INS）、基质金属蛋白酶9 （MMP9）、缺氧诱导因子-1α 亚基（HIF1A）、半胱氨酸天冬氨酸蛋白酶3（CASP3）、B淋巴细胞瘤-2（BCL2）、核心靶点为肿瘤蛋白p53（TP53）、FOS原癌基因（FOS）、前列腺素内过氧化物合酶2（PTGS2） 等核心靶点。富集分析发现磷脂酰肌醇3激酶-蛋白激酶B（PI3K-Akt） 信号通路和缺氧诱导因子-1（HIF-1） 信号通路与黄精治疗HF密切相关。分子对接结果显示黄精主要活性成分与核心靶点具有较强的结合活性。结论：黄精中的芹菜素、β-谷甾醇、黄芩素、异甘草素、薯蓣皂苷等主要活性成分，通过作用于AKT1、TNF、MMP9、HIF1A、CASP3、BCL2等靶点，调控PI3K-Akt、HIF-1等信号通路发挥治疗HF的作用。

Abstract:

Abstract： Objective： To analyze the pharmacodynamic substances and mechanism of action of Polygonati Rhizoma in treating heart failure （HF） using network pharmacology and molecular docking technology. Methods： Potential active components of Polygonati Rhizoma and their corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. HF-related targets were obtained from the GeneCards and OMIM databases. The intersection of potential component targets of Polygonati Rhizoma and HF-related targets yielded potential targets for Polygonati Rhizoma in treating HF. The STRING database was used to construct a protein-protein interaction （PPI） network， from which core targets and major active components were screened. The DAVID database was used for Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis of the intersection targets. Finally，AutoDock Tools software was employed for molecular docking to evaluate the binding activity of major active components with core targets. Results： A total of 15 active components of Polygonati Rhizoma and 87 potential targets for treating HF were screened. Network analysis of "drug-active components-targets" identified major active components， including apigenin， β-sitosterol， baicalein， isoliquiritigenin， and dioscin. PPI network analysis identified core targets such as AKT serine/threonine kinase 1 （AKT1）， tumor necrosis factor （TNF）， insulin （INS）， matrix metalloproteinase 9 （MMP9）， hypoxiainducible factor 1-alpha （HIF1A），caspase 3 （CASP3），B-cell lymphoma 2 （BCL2），tumor protein p53 （TP53）， Fos proto-oncogene （FOS），and prostaglandin-endoperoxide synthase 2 （PTGS2）. Enrichment analysis revealed that the phosphatidylinositol 3-kinase-protein kinase B （PI3K-Akt） signaling pathway and the hypoxia-inducible factor- 1 （HIF-1） signaling pathway are closely related to the treatment of HF by Polygonati Rhizoma. Molecular docking results showed strong binding activity between the major active components of Polygonati Rhizoma and the core targets. Conclusion： The major active components in Polygonati Rhizoma， such as apigenin， β -sitosterol， baicalein， isoliquiritigenin， and dioscin， exert therapeutic effects on HF by acting on targets including AKT1， TNF， MMP9， HIF1A，CASP3，and BCL2，thereby regulating signaling pathways such as PI3K-Akt and HIF-1.