基于网络药理学探讨牛大力治疗抑郁症的活性成分及分子机制

Study on the active ingredients and molecular mechanisms of Millettia speciosa Champ.in the treatment of depressionbased on network pharmacology

目的:采用网络药理学方法研究牛大力治疗抑郁症的活性成分及作用机制。方法:借助中药系统药理学数据库分析平台(TCMSP)与文献资料检索筛选出牛大力活性成分;运用Swiss Target Prediction预测成分靶点,并从Gene Cards数据库中预测抑郁症相关靶点;同时,采用Cytoscape 3.2.1软件构建活性成分-靶点-疾病网络图;String数据库和DAVID数据库进行蛋白质相互作用分析及基因本体(GO)、KEGG通路富集分析,再根据网络分析结果筛选活性成分和关键靶点,用Surflex软件进行分子对接。结果:本次研究共筛选出牛大力活性成分43个,主要包括补骨脂二氢黄酮、甘草酸、槲皮素等化学成分;关键靶点10个主要包括大麻素CB1受体(Cnr1)、5-羟色胺1b受体(Htr1b);关键通路涉及神经配体-受体相互作用信号通路、CAMP信号通路。分子对接结果显示甘草酸、槲皮素、补骨脂二氢黄酮与Cnr1、多巴胺D3受体(Drd3)、促性腺激素释放激素受体(Gnrhr)、粉状蛋白前体蛋白(App)等靶点蛋白有较好的结合能力。结论:采用网络药理学方法预测牛大力治疗抑郁症的相关活性成分及潜在作用机制,为牛大力的临床应用及实验研究提供理论依据。

Objective:To explore the mechanism of Millettia speciosa Champ.in the treatment of depression based on network pharmacology.Methods:The active components of Millettia speciosa Champ.were searched and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and literature data.Prediction of component targets was achieved using Swiss Target Prediction and depression related targets were predicted from the Gene Cards database.Meanwhile,the active component-target-disease network was constructed by Cytoscape 3.2.1 software.String database and DAVID database were used for protein-protein interaction analysis,gene ontology(GO)enrichment analysis,and KEGG pathway enrichment analysis.According to the results of network analysis,the components and targets were screened and molecular docking was performed by Surflex software.Results:43 active components of Millettia speciosa Champ.were screened and 10 key targets including Cnr1,Htr1b,etc.The critical pathway involves theneuroactive ligand-receptor interaction and the CAMP signaling pathway.The molecular docking results showed that ethyl linolenate,glycyrrhizic acid,quercetin andBavachin had a good binding ability with Cnr1,Drd3,Gnrhr,App and other target proteins.Conclusion:In this study,a network pharmacology analysis method was used to predict the related active ingredients and the potential mechanism of action of Millettia speciosa Champ.in the treatment of depression,to provide a theoretical basis for the clinical application and experimental research of Millettia speciosa Champ.