基于网络药理学和分子对接研究“白花蛇舌草-半枝莲”药对治疗前列腺癌的作用机制

Analysis of Mechanisms of Hedyotis Diffusa-Scutellaria Barbata Herb Pair in the Treatment of Prostatic Cancer Based on Network Pharmacology and Molecular Docking

目的:通过网络药理学、分子对接方法研究“白花蛇舌草-半枝莲”药对对前列腺癌的潜在药理作用靶点及作用机制,为基础研究及临床应用提供依据。方法:利用TCMSP数据库,查找到“白花蛇舌草-半枝莲”药对的药物活性成分,并对其进行靶点预测,预测数据库为SwissTargetPrediction。同时,应用DisGeNet、GeneCards、OMIM及DRUGBANK数据库获取前列腺癌疾病靶点,利用Uniprot数据库对靶点进行校正;并利用VENNY 2.1网站绘制韦恩图,取得化合物-疾病交集。分别使用Cytoscape3.7.2、STRING数据库平台构建活性成分-靶点网络图和共有靶点蛋白互作网络(PPI),通过相互关系大小来确定核心靶标。利用DAVID对关键靶点进行GO和KEGG富集分析。对主要活性成分与靶点,使用AutoDock软件进行分子对接。结果:“白花蛇舌草-半枝莲”药对共收集到33个有效成分,网络分析得到38个靶点基因与前列腺癌密切相关,这些靶点主要涉及信号转导、凋亡过程的正向调控、蛋白酪氨酸激酶活性,并主要富集在PI3K-Akt信号通路上。分子对接结果表明,“白花蛇舌草-半枝莲”药对主要活性成分与ESR1、CCND1和SRC具有良好的结合能力。结论:“白花蛇舌草-半枝莲”药对治疗前列腺癌具有多成分、多靶点、多途径的特点,为基础研究和临床应用提供了科学依据。

Objective:To study the potential pharmacological target and mechanism of Hedyotis diffusa-Scutellaria barbata herb pair(HS)on prostatic cancer based on network pharmacology and molecular docking methods,in order to provide basis for its basic research and clinical application.Methods:The active ingredients of HS were obtained from TCMSP,and these active ingredients were predicted by SwissTargetPrediction database.At the same time,the disease target of prostatic cancer was obtained by OMIM,DisGeNet,DRUGBANK and GeneCards database,and the target was corrected by Uniprot database,and the Wayne diagram was drawn by VENNY2.1 website to obtain the ingredient-disease intersection.The ingredient-target network diagram was constructed by Cytoscape 3.7.2,and the protein-protein interaction network(PPI)was constructed by String database platform,and the core targets were selected according to the correlation.DAVID was used to analyze the enrichment of key targets by GO and KEGG.AutoDock software was used for verification of main active compounds via molecular docking with targets.Results:A total of 33 active ingredients of HS were collected.Network analysis showed that 57 target genes were closely related to prostatic cancer.These targets were mainly related to the positive regulation of kinase activity,transmembrane receptor protein tyrosine kinase signal pathway and cell proliferation,and were mainly enriched in PI3K-Akt signal pathway.The results of molecular docking showed that the main active ingredients of HS have good binding ability with ESR1,CCND1 and SRC to the core targets.Conclusion:This study reflects the characteristics of HS on“multiingredient-multi-target-multi-pathway”and provides a scientific basis for its treatment of prostatic cancer.