基于网络药理学与分子对接探讨黄芪桂枝五物汤及芍药甘草汤治疗糖尿病周围神经病变“同病异治”的作用机制

Exploration on Mechanism of “Different Treatment for the Same Disease” of Huangqi Guizhi Wuwu Decoction and Shaoyao Gancao Decoction in Treating Diabetic Peripheral Neuropathy Based on Network Pharmacology and Molecular Docking

摘要: 目的：基于网络药理学与分子对接探讨黄芪桂枝五物汤及芍药甘草汤治疗糖尿病周围神经病变“同病异治”的作用机制。方法：检索TCMSP数据库获取黄芪桂枝五物汤、芍药甘草汤中中药活性成分，预测相关作用靶点，利用Uniprot数据库转换靶点基因信息；应用Drugbank、OMIM和GeneCards数据库筛选糖尿病周围神经病变靶点信息；利用微生信平台绘制韦恩图，将两方中获取的靶点蛋白与疾病靶点进行汇总取交集，获取三者共有的靶点；导入STRING数据库构建核心蛋白质相互作用图，通过Cytoscape 3.7.0构建“单味中药–活性成分–靶点”网络图；根据度值筛选黄芪桂枝五物汤、芍药甘草汤治疗DPN的关键靶点基因，取交集靶点后应用David数据库进行GO和KEGG富集分析，运用微生信平台进行绘图；运用AutoDock Tools-1.5.7活性成分与关键靶点进行分子对接，运用Pymol软件可视化处理所获得的结果。结果：筛选后得到黄芪桂枝五物汤有效成分43种，芍药甘草汤活性成分92种，其中两方中共有的活性成分12种，获得作用靶点272个。“单味中药–活性成分–潜在靶点”网络图获取quercetin (槲皮素)、beta-sitosterol (β-谷甾醇)、kaempfrerol (山奈酚)等3个主要活性成分；PPI网络图中核心靶点为AKT1、TP53、JUN等3个主要核心靶点。GO功能富集分析得到细胞组成(CC) 67项、分子功能(MF) 153项、生物过程(BP) 642项；KEGG分析结果共179项，主要涉及癌症途径、糖尿病并发症AGERAGE信号通路、MAPK信号通路等信号通路。结论：黄芪桂枝五物汤及芍药甘草汤通过多种药物成分，调节多条信号通路，关联多个靶点，从而发挥对糖尿病周围神经病变的“同病异治”作用。

Abstract: Objective: To explore the mechanism of “treating the same disease with different prescriptions” of Huangqi Guizhi Wuwu Decoction and Shaoyao Gancao Decoction in the treatment of diabetic peripheral neuropathy based on network pharmacology and molecular docking. Methods: The active components of Huangqi Guizhi Wuwu Decoction and Shaoyao Gancao Decoction were obtained by searching databases, and the related action targets were predicted. The target gene information was converted using databases. The target information of diabetic peripheral neuropathy was screened using databases. The Venn diagram was drawn using the Microbiome platform to summarize and intersect the target proteins obtained from the two prescriptions with the disease targets, and the common targets of the three were obtained. The core protein interaction map was constructed by importing the database, and the “single herb-active component-target” network map was constructed. The key target genes of Huangqi Guizhi Wuwu Decoction and Shaoyao Gancao Decoction in the treatment of DPN were screened based on the degree value, and the intersection targets were obtained. The database was used for enrichment analysis, and the results were plotted using the Microbiome platform. Molecular docking was performed using the active components and key targets, and the results were visualized using software. Results: After screening, 43 active components of Huangqi Guizhi Wuwu Decoction and 92 active components of Shaoyao Gancao Decoction were obtained, among which 12 were common active components. A total of 272 action targets were obtained. The “single herb-active component-potential target” network map obtained three main active components: quercein, beta-sitostero and kaempfreroand. The core targets in the network map were three main core targets: AKT1, TP53 and JUN. Functional enrichment analysis obtained 67 items of cell composition (CC), 153 items of molecular function (MF), and 642 items of biological process (BP). A total of 179 items were analyzed, mainly involving cancer pathways, diabetic complications AGERAGE signaling pathways, MAPK signaling pathways, and other signaling pathways. Conclusion: Huangqi Guizhi Wuwu Decoction and Shaoyao Gancao Decoction exert the “treating the same disease with different prescriptions” effect on diabetic peripheral neuropathy through multiple drug components, regulating multiple signaling pathways, and associating multiple targets.