基于网络药理学的黄芪抗疲劳作用机制研究

Mechanism of anti-fatigue of Astragali Radix based on network pharmacology

目的基于网络药理学方法探讨黄芪抗疲劳可能的作用机制。方法根据课题组前期研究并结合中医药系统药理学数据库和分析平台(TCMSP)指认黄芪中的活性成分,采用Pharm Mapper网络服务器预测其作用靶点;在GeneCards、OMIM数据库中搜索抗疲劳靶点,采用Cytoscape 3.6.0软件构件黄芪活性成分-抗疲劳靶点网络;使用String数据库进行蛋白质-蛋白质相互作用分析,构建蛋白质-蛋白质相互作用网络,通过度值(degree)筛选关键靶点并进行归属;使用DAVID数据库对黄芪抗疲劳作用靶点进行基因本体(GO)富集分析和KEGG通路富集分析,以探究黄芪抗疲劳的作用机制。结果获得黄芪中11种活性成分,包括毛蕊异黄酮葡萄糖苷、毛蕊异黄酮、芒柄花苷、芒柄花素、异黄烷、紫檀烷6种黄酮类成分,黄芪皂苷Ⅰ、Ⅱ、Ⅲ、Ⅳ 4种皂苷类成分及蔗糖。黄芪抗疲劳作用预测靶点有76个,网络分析结果表明,黄芪主要涉及一氧化氮的生物合成、过氧化氢反应、棕色脂肪细胞分化的正调节、活性氧代谢等生物过程,通过调节癌症通路,FoxO、磷脂酰肌醇3-激酶(PI3K)-蛋白激酶B(Akt)、低氧诱导因子-1(HIF-1)、血管内皮生长因子(VEGF)、丝裂原活化蛋白激酶(MAPK)、Ca^(2+)信号通路、氧化应激反应等来发挥抗疲劳作用。结论本研究体现了黄芪多成分-多靶点-多途径的作用特点,为进一步开展黄芪抗疲劳作用机制的研究提供了新思路和新方法。

Objective To explore the anti-fatigue mechanism of Astragali Radix based on network pharmacology.Methods The main active ingredients of Astragali Radix were obtained by TCMSP and the results of our previous work.GeneCards and OMIM were used to predict and screen the therapeutic targets of Astragali Radix.The Cytoscape 3.6.0 software was used to construct the active components-targets network of Astragali Radix.The protein interactions network was constructed using the String database and Cytoscape software.The GO and KEGG pathways involved in the targets were analyzed by using DAVID database.Results The results showed that 11 active components including six flavonoids(calycosin-7-O-β-D-glucoside,calycosin,ononin,formononetin,7,2′-dihydroxy-3,4-dimethoxyisoflavan,3-hydroxy-9,10-dimethoxypterocarpan),four saponins(astragalosideⅠ,Ⅱ,Ⅲ,Ⅳ)and sucrose and 76 targets of Astragali Radix were involved.The network analysis results showed that the process of nitric oxide biosynthesis,hydrogen peroxide reaction,positive regulation on brown adipocyte differentiation,and active oxygen metabolism were mainly involved by adjusting the cancer,FoxO,PI3 K-Akt,HIF-1,VEGF,MAPK and other signaling pathways to exert its antifatigue effect.Conclusion This study reflects the characteristics of multi-components,multi-targets,and multi-pathways of Astragali Radix,which provides new ideas and clues for further research on the mechanism of anti-fatigue effects of Astragali Radix.