基于网络药理学和分子对接技术的银柴胡解热作用机制探讨

目的 采用网络药理学与分子对接技术探讨银柴胡解热作用的机制。方法 借助中药系统药理学数据库与分析平台（TCMSP）、中医药整合药理学研究平台（TCMIP）和中药分子机制生物信息学分析工具（BATMAN-TCM）筛选银柴胡活性成分和相关作用靶点；使用GeneCards、OMIM和TTD数据库筛选发热相关靶点；通过STRING数据库构建活性成分靶点与发热疾病靶点蛋白质-蛋白质相互作用（PPI）网络；利用Cytoscape软件的Network Analysis插件对获得的PPI网络进行拓扑分析，筛选核心节点；使用Venny软件获得银柴胡活性成分靶点、发热疾病靶点和核心节点的交集靶点，并通过进一步的拓扑分析筛选得到关键成分和关键靶点；通过DAVID数据库进行基因本体（GO）功能注释和京都基因与基因组百科全书（KEGG）通路富集分析；利用Schr?dinger软件对关键靶点与对应的关键成分进行分子对接。结果 银柴胡解热关键成分为银柴胡胺D和银柴胡新木质素-β-D-葡萄糖苷A~D，71个关键靶点主要包括促丝裂原活化蛋白激酶10（MAPK10）、蛋白激酶B1（Akt1）、热休克蛋白90AA1（HSP90AA1）、细胞周期蛋白依赖性激酶2（CDK2）、转化蛋白p21（HRAS）、血管内皮生长因子受体2（KDR）、原癌基因受体酪氨酸激酶（KIT）等；KEGG富集的67条通路主要包括Rap1信号通路、Toll样受体信号通路、肿瘤坏死因子（TNF）信号通路、Ras信号通路等；分子对接结果表明，银柴胡新木质素-β-D-葡萄糖苷A与KDR，银柴胡新木质素-β-D-葡萄糖苷C与CDK2、HRAS和HSP90AA1，银柴胡新木质素-β-D-葡萄糖苷D与Akt1、HRAS和KIT具有良好的结合能力。结论 银柴胡解热作用机制可能与抗炎、抗过敏、调节新陈代谢、促进免疫调节等过程有关。

Mechanism of Heat-clearing Effect of Stellariae Radix Based on Network Pharmacology and Molecular Docking

Objective To explore the potential mechanism of the heat-clearing effect of Stellariae Radix by virtue of network pharmacology and molecular docking.Methods The active components and related targets of Stellariae Radix were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP), and Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM).The potential targets associated with fever were retrieved from GeneCards, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD).STRING was employed to build the protein-protein interaction (PPI) network for the targets of the active components and fever.The topology of the PPI network was analyzed by the Network Analysis plug-in of Cytoscape and the core nodes were screened out.Venny was employed to identify the common targets shared by active components, fever, and core nodes, and the key components and key targets were screened by further topological analysis.Gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out with DAVID.Schr?dinger was used for the molecular docking between the key targets and the corresponding key components.Results Five key active components for the heat-clearing effect of Stellariae Radix were dichotomine D and dichotomosides A-D.The 71 key targets were mitogen-activated protein kinase 10 (MAPK10), protein kinase B1 (Akt1), heat shock protein HSP 90-alpha (HSP90AA1), cyclin-dependent kinase 2 (CDK2), transforming protein p21 (HRAS), vascular endothelial growth factor receptor 2 (KDR), proto-oncogene c-kit (KIT), etc.The 67 enriched KEGG pathways mainly included Rap1, Toll-like receptor, tumor necrosis factor (TNF), and Ras signaling pathways.The results of molecular docking showed that dichotomoside A had good binding ability to KDR, dichotomoside C to CDK2, HRAS, and HSP90AA1, and dichotomoside D to Akt1, HRAS, and KIT.Conclusion Stellariae Radix may exert heat-clearing effect by reducing inflammation, alleviating allergy, regulating metabolism, and promoting immune regulation.