基于网络药理学及分子对接探讨灵泽片治疗前列腺良性增生的作用机制

A study on the mechanism of treating benign prostatic hyperplasia with the Lingze tablets based on network pharmacology and molecular docking

目的:采用网络药理学方法探讨灵泽片治疗前列腺良性增生疾病的作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)、中医药整合药理学研究平台(TCMIP)对药物活性成分进行查找与筛选,获得药物的作用靶点。利用GeneCards、TTD、DISGENET数据库获取疾病靶点。利用Venny 2.1.0平台绘制韦恩图,获取疾病、药物交集靶点。用Cytoscape3.8.2软件绘制药物的有效活性成分-作用靶点网络。利用STRING平台构建疾病、药物交集靶点的相互作用网络。用DAVID数据库对疾病、药物交集靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。采用AutoDock Vina进行分子对接。结果:通过筛选得到445个药物作用靶点,1 338个疾病相关靶点,125个交集靶点;腺苷、松属素、去氧泽泻醇A、泽泻醇A、泽泻醇A酯等为关键成分,热休克蛋白90α家族A类成员1(Heat Shock Protein 90 Alpha Family Class A Member 1,HSP90AA1)、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、SRC原癌基因(SRC Proto-Oncogene,SRC)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)3、雌激素受体1(Estrogen Receptor 1,ESR1)等为核心靶点;GO分析得到557条生物过程、70项细胞组分,112项分子功能;KEGG分析显示灵泽片主要通过调控MAPK信号通路、松弛素信号通路、雌激素信号通路、白细胞介素(Interleukin,IL)-17信号通路、细胞凋亡等来治疗前列腺良性增生。分子对接结果显示,核心靶点与关键成分对接良好。结论:灵泽片可通过多成分、多靶点、多途径治疗前列腺良性增生,为临床治疗前列腺良性增生提供依据与思路。

Objective:To investigate the mechanism of action of the Lingze tablets(灵泽片)in the treatment of benign prostatic Ohyperplasia(BPH)by network pharmacology.Methods:TCMSP and TCMIP databases were used to find and screen the active ingredients of the drug to obtain the targets of action of the drug.GeneCards,TTD and DISGENET databases were used to obtain the disease targets.Venny 2.1.0 platform was used to draw Venn diagrams to obtain the targets of disease-drug intersection.Cytoscape 3.8.2 platform was used to draw Venn diagrams to obtain the network of the disease-drug intersection targets.STRING platform was used to construct the interaction network of the targets of the disease-drug intersection.GO and KEGG pathway enrichment analyses of the disease-drug intersection targets was performed using DAVID database.Molecular docking was performed using AutoDockVina.Results:A total of 445 drug action targets,1338 disease-related targets,and 125 intersection targets were obtained by screening.Adenosine,pine genistein,deoxynivalenol A,alizarinol A,and alizarinol A ester were key components,HSP90AA1,AKT1,SRC,MAPK3,and ESR1 were core targets.GO analysis yielded 557 biological processes,70 cellular components,and 112 molecular functions.KEGG analysis showed that the Lingze tablets mainly treated BPH by regulating MAPK signaling pathway,relaxin signaling pathway,estrogen signaling pathway,IL-17 signaling pathway,apoptosis,etc..The molecular docking results showed that the core targets dovetailed well with the key components.Conclusion:The Lingze tablets can treat benign prostatic hyperplasia through multi-component,multi-target and multi-pathway,providing the basis and ideas for clinical treatment of BPH.