基于网络药理学及分子对接研究夏枯草治疗乳腺囊性增生病的药理作用机制  

Pharmacological mechanism of prunella vulgaris in treating breast cystic hyperplasia based on network pharmacology and molecular docking

作　　者：钟想 尹旭 何天翼 杜佳尚 何志贤[3] ZHONG Xiang;YIN Xu;HE Tianyi;DU Jiashang;HE Zhixian(Medical School of Nantong University,Nantong,Jiangsu 226000,China;Nanjing Medical University,Nanjing,Jiangsu 210000,China;Affiliated Hospital of Nantong University,Nantong,Jiangsu 226000,China)

机构地区：[1]南通大学附属医院甲乳外科/南通大学医学院,江苏南通226000 [2]南京医科大学,江苏南京210000 [3]南通大学附属医院甲乳外科,江苏南通226000

出　　处：《现代医药卫生》2022年第24期4156-4163,共8页Journal of Modern Medicine & Health

基　　金：江苏省妇幼健康科研项目(F201953);江苏省南通市级基础科学研究项目(JC2020067)。

摘　　要：目的联合运用网络药理学和分子对接技术研究夏枯草治疗乳腺囊性增生病的药理作用机制。方法通过美国TCMSP数据库搜索夏枯草中有效成分信息及其对应的作用研究靶点,运用GeneCards、OMIM、PharmGkb、DrugBank数据库获取相关乳腺囊性增生病的临床疾病靶点。将乳腺囊性增生病对应的相关疾病靶点和夏枯草潜在作用靶点相互映射取一交集,并绘制韦恩图。运用STRING数据库和Cytoscape 3.9.0软件对疾病和药物共同靶点进行蛋白质互作网络分析,并应用R软件对交集基因进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路分析;通过Cytoscape 3.9.0软件构建疾病-中药活性成分-靶点网络图。运用Sybyl软件以分子对接的形式验证夏枯草活性成分与乳腺囊性增生病核心基因靶点的相互作用。结果共筛选出夏枯草11个活性成分及186个基因靶点,2699个乳腺囊性增生病基因靶点。141个药物和疾病的共同靶点,24个核心基因;主要涉及氧化应激反应、抗炎、调节免疫功能等多个生物学过程,主要涉及的信号通路包括环磷酸腺苷信号通路、晚期糖化终末产物-晚期糖化终末产物受体信号通路、肿瘤坏死因子信号通路、磷酸肌醇-3激酶/蛋白激酶B信号通路、白细胞介素-17信号通路等。夏枯草活性成分与乳腺囊性增生病的相关疾病靶点可通过氢键结合,进而相互作用。结论揭示了夏枯草可能通过其主要活性成分与丝/苏氨酸蛋白激酶1、环加氧酶2、丝裂原激活蛋白激酶8、酪氨酸激酶受体2靶蛋白结合发挥在乳腺囊性增生病中的疗效,并通过环磷酸腺苷信号通路、晚期糖化终末产物-晚期糖化终末产物受体信号通路、肿瘤坏死因子信号通路实现的,为进一步药理学实验提供了科学的理论依据。Objective To explore the pharmacological mechanism of prunella vulgaris in treating breast cystic hyperplasia by combining network pharmacology and molecule docking.Methods The information of active ingredients in prunella vulgaris and their corresponding targets were searched by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database of the United States.GeneCards,Online Mendelian Inheritance in Man(OMIM),PharmGkb and DrugBank databases were used to obtain clinical disease targets related to breast cystic hyperplasia.The intersection of related disease targets corresponding to breast cystic hyperplasia and potential targets of prunella vulgaris was taked and the Wayne diagram was drawn.The Search Tool for the Retrieval of Interacting Genes(STRING)database and Cytoscape 3.9.0 software were used for protein interaction network analysis of disease and drug common targets,and R software was used for gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.The disease-TCM active ingredient-target network diagram was constructed by Cytoscape 3.9.0 software.The Sybyl software was used to test the interaction between active ingredients of prunella vulgaris and core gene targets of breast cystic hyperplasia by molecular docking.Results A total of 11 active ingredients,186 gene targets of prunella vulgaris,2,699 gene targets of breast cystic hyperplasia,141 common targets of drugs and diseases,and 24 core genes were screened.And they mainly involved multiple biological processes such as oxidative stress response,anti-inflammatory,and immune function regulation,and mainly involved several signaling pathways,including cyclic adenosine phosphate signaling pathway,advanced glycation end products-advanced glycation end products receptor signaling pathway,tumor necrosis factor signaling pathway,phosphoinositol-3 kinase/protein kinase B signaling pathway,interleukin-17 signaling pathway and so on.The active ingredients of prunella vulgaris

关 键 词：夏枯草 乳腺囊性增生病 网络药理学 分子对接 核心基因 活性成分 

分 类 号：R655.8[医药卫生—外科学] R282.71[医药卫生—临床医学]