基于UPLC-Q-TOF-MS/MS和网络药理学方法探讨短梗五加改善失眠的潜在药效成分及作用机制

目的:研究短梗五加改善失眠的药效物质基础及潜在的作用机制。方法:运用UPLC-Q-TOF-MS/MS技术,结合文献,对短梗五加化学成分进行分析鉴定,使用SwissADME对成分进行筛选,通过 Swiss Target Prediction数据库预测活性成分潜在靶点,GeneCards、DRUGBANK、OMIM和DisGeNET数据库搜集疾病靶点,使用VENNY软件收集成分-靶点交集,Cytoscape软件构建靶点蛋白相互作用网络,利用DAVID数据库进行GO和KEGG富集,使用微生信平台进行可视化分析。随后利用Cytoscape构建成分-靶点-通路图,运用AutoDock Vina和Pymol软件进行分子对接。进一步建立斑马鱼睡眠剥夺模型对活性成分进行验证。结果:异嗪皮啶、金合欢素、东莨菪碱内酯、丁香酸、川芎哚等16个成分为短梗五加改善睡眠药效成分,可能作用于ESR1、AKT1、EGFR、PTGS2和PPARG等靶点,成分与靶点结合能小于-4.25kJ·mol^-1的占总数94%,显示良好的结合活性。短梗五加通过雌激素、PI3K-Akt、ErbB、HIF-1等信号通路改善失眠。总提物、金合欢素、异嗪皮啶和东莨菪碱内酯均可改善失眠并具有一定的镇静作用(P＜0.01,P＜0.05)。结论:短梗五加改善失眠可能是通过多靶点、多成分起作用,本研究为产品的质量评价及深度开发提供科学依据。

Study on the potential pharmacodynamic components and mechanism of Eleutherococcus sessiliflorus in improving insomnia based on UPLC-Q-TOF-MS/MS and network pharmacology

OBJECTIVE Study on the pharmacodynamic material basis and potential mechanism of Eleutherococcus sessiliflorus in improving insomnia.METHODS By referring to UPLC-Q-TOF-MS/MS information and literature data,the chemical components of Eleutherococcus sessiliflorus were analyzed and identified.The components were screened by SwissADME,and the potential targets of active components of Eleutherococcus sessiliflorus were predicted by Swiss Target Prediction database.GeneCards,DRUGBANK,OMIM and DisGeNET databases were used to collect disease targets.VENNY Software was used to collect the intersection of components and targets.Cytoscape software was used to construct the interaction network of target proteins.DAVID database was used to enrich GO and KEGG,and bioinformatics platform was used for visual analysis.Cytoscape was then used to construct the component-target-pathway diagram.Molecular docking was performed using AutoDock Vina and Pymol.The sleep deprivation model of zebra fish was further established to verify the active components.RESULTS Sixteen components such as isofraxidin,acacetin,scopoletin,syringic acid,perlolyrine,et al were screened as improving insomnia components of Eleutherococcus sessiliflorus,which may act on ESR1,AKT1,EGFR,PTGS2 and PPARG targets.94% of the total binding energy was less than -4.25 kJ·mol^-1,showing good binding activity.Eleutherococcus sessiliflorus participate in regulation of estrogen signaling pathway,PI3K-Akt signaling pathway,ErbB signaling pathway,HIF-1 signaling pathway improve insomnia.The total extract,acacetin,isofraxidin and scopoletin could improve insomnia and had a certain sedative effect(P<0.01,P<0.05).CONCLUSION Eleutherococcus sessiliflorus may improve insomnia through multiple targets and components.This study provides scientific basis for product quality evaluation and further development.