世界中医药

目的：基于网络药理学方法和分子对接技术，探讨补阳还五汤有效成分治疗糖尿病脑病潜在作用机制。方法：从中药系统药理学数据库与分析平台（TCMSP）和中科院化学专业数据库筛选出补阳还五汤有效化学成分及其靶点，通过GeneCards、在线人类孟德尔遗传（OMIM）数据库收集糖尿病脑病靶点，运用STRING数据库构建蛋白质-蛋白质相互作用（PPI）网络图并通过Cytoscape 3.8.0软件中CytoNCA插件筛选关键靶点。利用ClusterProfiler程序包进行基因本体（GO）和京都基因和基因组百科全书（KEGG）富集分析，并通过Cytoscape 3.8.0软件构建补阳还五汤药物-成分-靶点-通路网络，最后利用AutoDock软件进行分子对接验证。结果：筛选得到补阳还五汤中活性成分108种，对应潜在靶点469个，网络图显示槲皮素、甘氨酸、洋川芎醌等是补阳还五汤治疗糖尿病脑病的关键成分，蛋白激酶、P53蛋白、肿瘤坏死因子等是该方治疗糖尿病脑病的关键靶点。GO富集分析显示该方可能通过对氧化应激的反应、对药物的反应、对金属离子的反应等生物过程发挥作用，与膜筏、膜微域、膜区域等细胞组分有关，与酰胺结合、DNA结合转录因子结合、肽结合等分子功能有关。KEGG富集分析显示主要与PI3K-AKT信号通路、MAPK信号通路有关。分子对接结果表明补阳还五汤中主要活性成分与核心作用靶点具有较为稳定的结合活性。结论：本研究初步揭示了补阳还五汤多成分、多靶点、多通路治疗糖尿病脑病的机制，为补阳还五汤的临床开发利用提供了依据。

English Summary:

To explore the possible mechanism of Buyang Huanwu Decoction in the treatment of diabetic encephalopathy(DE) based on network pharmacology and molecular docking.Methods:The active components and targets of Buyang Huanwu Decoction were selected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Chemistry Database of Chinese Academy of Sciences(CAS).The DE targets were collected from the GeneCards and Online Mendelian Inheritance in Man(OMIM).STRING was used to construct the protein-protein interaction(PPI) network，and the plugin CytoNCA of Cytoscape 3.8.0 was employed to screen the key targets.The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were conducted by Clusterprofiler.The drug-component-target-pathway network was constructed by Cytoscape 3.8.0，and AutoDock was adopted for molecular docking.Results:A total of 108 active components of Buyang Huanwu Decoction were obtained，corresponding to 469 potential targets.The drug-component-target-pathway network showed that quercetin，glycine and senkyunone were the key components of Buyang Huanwu Decoction in the treatment of DE，and protein kinase，P53 protein，and tumor necrosis factors were the key targets.GO enrichment analysis revealed that this prescription may exert the effect through processes such as acting on oxidative stress，drugs，and metal ions，involving the cell components of membrane raft，membrane microdomain and membrane region and the molecular functions of amide binding，DNA-transcription factor binding and peptide binding.KEGG enrichment analysis showed that PI3K-Akt and MAPK signaling pathways were mainly involved.Molecular docking indicated that the main active components in Buyang Huanwu Decoction had stable binding activity to the core action targets.Conclusion:This study revealed the mechanism of Buyang Huanwu Decoction in the treatment of DE，and provided a basis for the clinical development and utilization of the prescription.

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