基于网络药理学与分子对接技术探究菟丝子干预2型糖尿病的潜在作用机制

Exploring the potential mechanism of Cuscuta chinensis Lam.for the intervention in type 2 diabetes mellitus based on network pharmacology and molecular docking

目的:基于网络药理学与分子对接技术探究菟丝子干预2型糖尿病的潜在作用机制。方法:课题组前期采用液质联用技术分析鉴定出12种菟丝子提取液灌胃大鼠后血浆化学成分。通过PubChem、Swiss Target Prediction数据库获取入血成分作用靶点,与疾病靶点取交集。在此基础上进行共同靶点的蛋白质互作(protein-protein interaction,PPI)网络构建,并进行GO和KEGG富集分析,将核心成分与关键靶点进行分子对接验证。结果:获得111个潜在靶点;GO与KEGG富集分析显示菟丝子核心成分可能参与脂质和动脉粥样硬化、前列腺癌、癌症等信号通路来干预2型糖尿病;分子对接显示,菟丝子核心成分龙胆苦苷、染料木素和大豆苷元与关键靶点CYP19A1、EGFR、MMP2、MMP9和PTGS1具有较好的结合力。结论:菟丝子核心成分龙胆苦苷、染料木素和大豆苷元等作用于CYP19A1、EGFR、MMP2、MMP9和PTGS1等关键靶点,通过脂质和动脉粥样硬化、前列腺癌、癌症等信号通路来发挥干预2型糖尿病的作用,这为菟丝子的开发利用提供了理论依据。

Objective:To explore the potential mechanism of Cuscuta chinensis Lam.for the intervention in type 2 diabetes mellitus based on the network pharmacology and molecular docking.Methods:From our previous study,12 kinds of plasma chemical components were collected from Cuscuta chinensis Lam.treated rats and then identified by UPLC-Q-TOF-MS/MS.The database of PubChem and Swiss Target Prediction was queried to obtain the core target of the component of dodder entering blood,and the intersection with the disease targets was taken.The intersecting targets were subjected to protein-protein interaction(PPI)network construction,GO and KEGG enrichment analysis were carried out,and the key targets and active compounds were validated by molecular docking.Results:A total of 111 potential targets for the intervention in type 2 diabetes mellitus were obtained.GO and KEGG enrichment analysis suggested that the key compounds were closely related to lipid and atherosclerosis,prostate cancer,cancer pathway and other signaling pathways in intervention of diabetes.The binding sites between the active compounds of Cuscuta chinensis Lam.(Gentiopicrin,Genistein,Daidzein)and key targets(CYP19A1,EGFR,MMP2,MMP9 and PTGS1)were verified by molecular docking.Conclusions:The active components of Gentiopicrin,Genistein and Daidzein act on the key targets of YP19A1,EGFR,MMP2,MMP9 and PTGS1,which may be important mechanisms of Cuscuta chinensis Lam.for the intervention in type 2 diabetes mellitus.The lipid and atherosclerosis,prostate cancer,cancer pathway and other signaling pathways were involved in the intervention in diabetes.These provide a theoretical foundation for the development of Cuscuta chinensis Lam.