基于网络药理学和分子对接探讨苗药土大黄防治功能性子宫出血的作用机制  

Study on the mechanism of prevention and treatment of functional uterine bleeding by Rumei Radix et Rhizoma based on network pharmacology and molecular docking analysis

作　　者：卢旭 李玲 张宁 LU Xu;LI Ling;ZHANG Ning(College of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001,China)

机构地区：[1]贵州中医药大学药学院,贵州贵阳550025 [2]贵州中医药大学第一附属医院,贵州贵阳550001

出　　处：《现代药物与临床》2023年第7期1597-1605,共9页Drugs & Clinic

基　　金：贵州省教育厅自然科学研究项目(黔教合KY字[2021]203)。

摘　　要：目的利用网络药理学和分子对接的方法探讨苗药土大黄防治功能性子宫出血(DUB)的潜在作用机制。方法基于文献研究筛选得到土大黄主要活性成分,利用Swiss Target Prediction平台预测土大黄的作用靶点,利用OMIM、DrugBank、DisGeNet、GeneCards数据库确定DUB的疾病靶点,并通过Venny 2.1.0在线工具将其与土大黄靶点取交集后获得土大黄防治DUB的潜在作用靶点;在STRING数据库进行蛋白互作网(PPI)分析,结合Cytoscape 3.8.2软件筛选关键靶点。将筛选得到的交集靶点导入DAVID数据库进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。最后运用AutoDock Tools软件将筛选出的关键成分与关键靶点进行分子对接验证。结果结合文献研究与Swiss Target Prediction平台筛选得到药物活性成分26个,药物靶点392个,疾病靶点436个,共同靶点74个;经PPI及网络拓扑分析后,获取核心靶点7个,分别是信号转导和转录激活因子3(STAT3)、原癌基因酪氨酸蛋白激酶(SRC)、磷酸肌醇3-激酶调节亚基1(PIK3R1)、磷脂酰肌醇3-激酶催化亚基α(PIK3CA)、雌激素受体(ESR1)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、转录因子p65(RELA);经活性成分–核心靶点网络的构建及网络拓扑分析,得到土大黄防治DUB主要活性成分9个,分别是槲皮素、阿魏酸、豆蔻酸、羟基大黄素、决明柯酮、大黄素甲醚、委陵菜酸、大黄酚、3,4-二羟基苯甲酸乙酯;GO富集到基因功能303个(P<0.01),KEGG富集到基因通路122条(P<0.01),结果表明,土大黄防治DUB的作用机制是通过调节低氧诱导因子-1(HIF-1)、磷酸化磷脂酰肌醇-3-激酶(p-PI3K)–蛋白激酶B(Akt)等信号通路来发挥防治DUB的作用。分子对接验证结果显示,关键活性成分与核心靶点均可自发结合。结论初步揭示了土大黄防治DUB的有效成分和可能的作用机制,并为深入研究药效物质基础、作用机制以及临床应用提供了科学�Objective To explore the potential mechanism of Rumei Radix et Rhizoma in prevention of functional uterine bleeding(DUB)by network pharmacology and molecular docking methods.Methods The main active components of Rumei Radix et Rhizoma were screened based on literature study.The Swiss Target Prediction platform was used to predict the target of DUB,and the disease target was determined by OMIM,DrugBank,DisGeNet and GeneCards databases.The potential target of DUB control of Rumei Radix et Rhizoma was obtained by intersection of DUB target and Rumei Radix et Rhizoma target through Venny 2.1.0 online tool.Protein interaction network(PPI)analysis was performed on STRING database,combined with Cytoscape 3.8.2 software to screen key targets.The selected intersection targets were imported into DAVID database for GO biological function and KEGG enrichment analysis.Finally,AutoDock Tools software was used to verify the molecular docking between the selected key components and key targets.Results Based on literature study and Swiss Target Prediction platform,26 drug active ingredients,392 drug targets,436 disease targets,and 74 common targets were identified.After protein interaction analysis(PPI)and network topology analysis,7 core targets were obtained,which were STAT3,SRC,PIK3R1,PIK3CA,ESR1,AKT1,and RELA.Through the construction of the active ingredient-core target network and network topology analysis,9 main active ingredients of Rumei Radix et Rhizoma control DUB were obtained.They are quercetin,ferulic acid,myrianthic acid,citreorosein,torachrysone,physcion,tormentic acid,chrysophanol,ethyl 3,4-dihydroxybenzoate;GO enriched 303 gene functions(P<0.01),KEGG enriched 122 gene pathways(P<0.01).The results showed that the mechanism of DUB prevention and control was through the regulation of HIF-1,PI3K-Akt and other signaling pathways.The results of molecular docking showed that both the key active ingredient and the core target could spontaneously bind.Conclusion This study preliminarily revealed the effective components a

关 键 词：苗药土大黄 功能性子宫出血 网络药理学 分子对接 转录激活因子3 原癌基因酪氨酸蛋白激酶 磷酸肌醇3-激酶调节亚基1 

分 类 号：R285.5[医药卫生—中药学] R984[医药卫生—中医学]