基于网络药理学与实验验证探讨白芷方干预偏头痛大鼠有效成分及作用机制

Active Components and Mechanism of Baizhi Decocotion Against Migraine in Rats Based on Network Pharmacology and Experimental Verification

目的:基于网络药理学及体外实验验证,探讨白芷方(BZD)治疗偏头痛潜在机制及初步药效作用。方法:构建硝酸甘油致大鼠偏头痛模型,评价白芷方治疗偏头痛活性。通过在线数据库和文献检索收集复方活性成分、作用靶点和偏头痛相关疾病靶点,构建蛋白质相互作用网络(PPI),并利用DAVID数据库进行GO和KEGG富集分析,使用Cytoscape软件构建“活性成分-核心靶点-通路”网络;最后通过AutoDock软件将关键活性成分和关键潜在靶点进行分子对接,并进行可视化分析。结果:与模型组相比,白芷方可升高大鼠血清超氧化物歧化酶(SOD)水平,降低丙二醛(MDA)、一氧化氮(NO)水平;升高血浆内皮素(ET)水平,降低血浆降钙素基因相关肽(CGRP)水平;同时升高脑匀浆肾上腺素(EPI)、去甲肾上腺素(NE)、5-羟色胺(5-HT)水平,并且都存在显著性差异(P<0.01)。网络药理学结果显示,白芷方中天麻素、阿魏酸、欧前胡素、藁本内酯等20个关键活性成分通过作用于PTGS2、RELA、JUN、MMP9、TNF等关键潜在靶点,调控206个GO项目和109条信号通路发挥干预偏头痛的作用。分子对接结果表明,白芷方关键活性成分与靶点对接结果良好。结论:初步探讨了白芷方对偏头痛的药效作用和潜在机制,为临床应用白芷方治疗偏头痛提供新的理论依据。

Objective:To explore the potential mechanism and preliminary efficacy of BZD in the treatment of migraine based on network pharmacology and in vitro experimental verification.Methods:In order to evaluate the activity of BZD in the treatment of migraine,a rat migraine model induced by nitroglycerin was established.The active components and targets were collected through online database and literature search,PPI was constructed by STRNG,GO functional enrichment and KEGG pathway enrichment were analyzed by DAVID database,and“active components-key targets-pathways”network was constructed by Cytoscape.Finally,the key active components and key targets were docked by AutoDock,and could be visually analyzed.Results:Compared with the model group,BZF could increase the level of serum SOD,decrease the level of MDA and NO,increase the level of plasma ET,decrease the level of plasma CGRP,and increase the level of EPI,NE and 5-HT in brain homogenate.The network pharmacology showed that 20 key active components such as gastrodin,ferulic acid,ammidin and ligustilide could interfere with migraine by acting on key potential targets such as PTGS2,RELA,JUN,MMP9 and TNF,regulating 206 GO projects and 109 signal pathways.The results of molecular docking showed that the key active components of BZD had a good docking result with the targets.Conclusion:This study preliminarily discusses the preliminary efficacy and potential mechanism of BZF in the treatment of migraine,which provides a new theoretical basis for clinical application.