补阳还五汤治疗糖尿病周围神经病变的网络药理学分子机制研究

Study on the molecular mechanism of Buyang Huanwu Decoction in treating diabetic peripheral neuropathy by network pharmacology

关键词:  网络药理学  补阳还五汤  糖尿病周围神经病变  槲皮素  β-谷甾醇  通路

Key words:  network pharmacology  Buyang Huanwu Decoction  diabetic peripheral neuropathy  quercetin  β-sitosterol  pathway

摘要:

[目的] 采用网络药理学对补阳还五汤治疗糖尿病周围神经病变（DPN）的分子机制进行探讨。[方法] 利用中药系统药理学分析平台（TCMSP）数据库、化学专业数据库收集补阳还五汤中7味中药的相关化学成分及作用靶点，与Drugbank、GeneCards数据库获得的DPN疾病靶点相映射，得到补阳还五汤治疗DPN的潜在靶点；通过STRING在线数据库得到蛋白互作关系并筛选出关键靶点，进而运用Cytoscape软件构建蛋白相互作用（PPI）网络和"补阳还五汤-活性成分-关键作用靶点"网络；使用R软件对补阳还五汤的关键作用靶点进行GO富集分析和KEGG通路富集分析，并构建"补阳还五汤-活性成分-靶点-KEGG通路"多维网络图。[结果] 筛选得到补阳还五汤81个活性成分和238个作用靶点，DPN疾病相关靶点4 334个，补阳还五汤治疗DPN的关键靶点124个，槲皮素（quercetin）、β-谷甾醇（beta-sitosterol）、黄芩素（baicalein）等12个成分具有潜在抗DPN活性，其可能作用于丝裂原活化蛋白激酶1（MAPK1）、SRC、JUN、肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）等靶点，通过AGE-RAGE信号通路、TNF信号通路、HIF-1信号通路等发挥治疗DPN的作用。[结论] 补阳还五汤通过多成分、多靶点、多途径起到干预治疗DPN的作用，为补阳还五汤治疗DPN的基础和临床研究提供新方向。

Abstract:

[Objective] To explore the molecular mechanism of Buyang Huanwu Decoction (BYHWD) in treating diabetic peripheral neuropathy by network pharmacology.[Methods] The related chemical components and action targets of seven Chinese medicines in BYHWD were collected by TCMSP database and chemistry professional database,and mapped with DPN disease targets obtained from Drugbank and GeneCards database to obtain potential targets of BYHWD in treating DPN. The protein interaction relationship is obtained through the STRING online database and the key targets are screened out,and then the PPI network and the "BYHWD-active components-key action targets" network are constructed by using Cytoscape software. GO enrichment analysis and KEGG pathway enrichment analysis were carried out on the key action targets of BYHWD by using R software,and the multidimensional network diagram of "BYHWD-active components-targets-KEGG Pathway" was constructed.[Results] The 81 active components and 238 action targets of BYHWD were screened,4 334 targets related to DPN diseases and 124 key targets of BYHWD in treating DPN. Twelve components such as quercetin,β-sitosterol and baicalein have potential anti-DPN activities. It may act on MAPK1,SRC,JUN,TNF,IL-6 and other targets,and play a role in treating DPN through AGE-RAGE signal pathway,TNF signal pathway,HIF-1 signal pathway,etc.[Conclusion] BYHWD plays an intervention role in treating DPN through multi-components,multi-target and multi-pathway interaction,which provides a new direction for the basic and clinical research of BYHWD in the treatment of DPN.