基于网络药理学的丹白颗粒治疗盆腔炎性疾病作用机制研究  

Mechanism of Danbai Granules in the Treatment of Pelvic Inflammatory Disease Based on Network Pharmacology

作　　者：翟弋焱 陈美琳 王伟 时锐 黄佳奇 张景媛 张繁芹 吴嘉瑞[1] ZHAI Yiyan;CHEN Meilin;WANG Wei;SHI Rui;HUANG Jiaqi;ZHANG Jingyuan;ZHANG Fanqin;WU Jiarui(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China;State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine,Lunan Pharmaceutical Group Co.,Ltd,Shandong Linyi 276000,China)

机构地区：[1]北京中医药大学中药学院,北京100029 [2]鲁南制药集团股份有限公司中药共性技术国家重点实验室,山东临沂276000

出　　处：《中国医院用药评价与分析》2023年第6期641-647,共7页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：国家自然科学基金项目(No.82074284);国家中医药传承创新团队子项目(No.ZYYCXTD-C-202005-10);北京中医药大学与鲁南厚普制药有限公司联合项目(No.BUCM-2022-JS-FW-034)。

摘　　要：目的:探讨丹白颗粒治疗盆腔炎性疾病的活性成分及其作用机制。方法:从中国知网、PubMed、中药系统药理学数据库与分析平台和GeneCards等数据库查询丹白颗粒中药物的化学成分及对应靶点和盆腔炎性疾病的相关靶点。取化学成分靶点与疾病靶点交集使用STRING数据库分析,上述分析结果采用Cytoscape软件绘制丹白颗粒成分-靶点图、蛋白质-蛋白质相互作用网络图等。通过R语言对交集靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。最后通过AutoDockTools软件进行分子对接的验证。结果:通过筛选获得丹白颗粒中70个化合物与377个化合物靶点,240个化合物与疾病交集靶点。根据相关参数进一步筛选得到关键靶点磷脂酰肌醇3激酶催化亚单位α异构体(PIK3CA)、肉瘤基因(SRC)、肿瘤蛋白53(TP53)、热休克蛋白90α(HSP90AA)、蛋白激酶B1(Akt1)、丝裂原活化蛋白激酶3(MAPK3)、丝裂原活化蛋白激酶1(MAPK1)、雌激素受体1(ESR1)、表皮生长因子受体(EGFR)、肿瘤坏死因子α(TNF-α)、v-rel网状内皮细胞过多症病毒癌基因同源物A(RELA)和白细胞介素6(IL-6)。富集分析结果显示,获得186条KEGG通路和3730条GO功能条目。GO功能条目又包含有3324条生物过程相关条目,166条细胞成分和240条分子功能相关条目。分子对接验证结果显示,槲皮素、木犀草素、山柰酚和柚皮素等化合物与SRC、TP53、HSP90AA、Akt1、MAPK1、ESR1、EGFR、TNF-α和IL-6有较强的结合能力。结论:丹白颗粒可能是通过核因子κB信号通路、MAPK信号通路和PI3K-Akt信号通路等通路作用于TNF-α、IL-6和EGFR等关键靶基因,发挥其治疗盆腔炎性疾病的作用。OBJECTIVE:To analyze the active components and mechanism of Danbai granules in the treatment of pelvic inflammatory diseases.METHODS:CNKI,PubMed,traditional Chinese medicine systems pharmacology database and analysis platform,GeneCards and other databases were retrieved to collect the corresponding targets and related targets of pelvic inflammatory disease.The intersection of chemical component targets and disease targets was analyzed using STRING database.The above analysis results were based on Cytoscape to construct the composition-target map and protein-protein interaction network map of Danbai granules.Cytoscape was used to draw the composition-target map and protein-protein interaction network map of Danbai granules.The gene ontology(GO)function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed for intersection targets by using R language.The molecular docking was verified by AutoDockTools software.RESULTS:Totally 70 compounds and 377 compound targets,240 compound and disease intersection targets in Danbai granules were obtained by screening.According to relevant parameters,the key targets of Phosphatidylinositol-3-kinase catalytic subunit alpha isoform(PIK3CA),sarcoma gene(SRC),tumor protein 53(TP53),heat shock protein 90α(HSP90AA),protein kinase B1(Akt1),mitogen activated protein kinase 3(MAPK3),MAPK1,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),tumor necrosis factorα(TNF-α),v-rel reticuloendotheliosis viral oncogene homolog A(RELA)and interleukin 6(IL-6)further screened.Enrichment analysis showed that 186 KEGG pathways and 3730 GO functional items were obtained.GO function entries contained 3324 items related to biological processes,166 items related to cell components,and 240 items related to molecular functions.Results of molecular docking verification showed that quercetin,luteolin,kaempferol,naringenin and other compounds had strong binding ability with SRC,TP53,HSP90AA,Akt1,MAPK1,ESR1,EGFR,TNF-αand IL-6.CONCLUSIONS

关 键 词：丹白颗粒 盆腔炎 网络药理学 分子对接 作用机制 

分 类 号：R932[医药卫生—生药学] R96[医药卫生—药学]