文献类型：期刊文献

中文题名：基于网络药理学和分子对接探讨少腹逐瘀汤治疗EMT痛经的作用机制

英文题名：Mechanism of Shaofu Zhuyu Decoction in treatment of EMT induced dysmenorrhea based on network pharmacology and molecular docking

作者：陈元欢[1];张作良[1];武权生[1];冯鹏[1];乔新颖[1];张小花[1];毛海燕[1];蔡爽[1];周小静[1]

第一作者：陈元欢

机构：[1]甘肃中医药大学,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2021

卷号：46

期号：24

起止页码：6484

中文期刊名：中国中药杂志

外文期刊名：China Journal of Chinese Materia Medica

收录：CSTPCD;;Scopus;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；PubMed;

基金：国家自然科学基金项目(81760879)。

语种：中文

中文关键词：少腹逐瘀汤;子宫内膜异位症痛经;网络药理学;作用机制

外文关键词：Shaofu Zhuyu Decoction;endometriosis induced dysmenorrhea;network pharmacology;mechanism of action

摘要：借助中药系统药理数据库和分析平台(TCMSP)、BATMAN-TCM数据库(Bioinformatics Analysis Tool for Molecular Mechanismof Traditional Chinese Medicine)对少腹逐瘀汤的有效成分及靶点进行检索,于比较毒物基因组学数据库(Comparative Toxicogenomics Database, CTD)、治疗靶点数据库(Therapeutic Target Database, TTD)、人类基因数据库(The Human Gene Database, GeneCards)、疾病相关的基因与突变位点数据库(DisGeNET)中,分别以"endometriosis""dysmenorrhea"为关键词,获取子宫内膜异位症和痛经的相关靶点。通过Cytoscape 3.8.0构建"中药-有效成分-治疗靶点"网络。借助STRING 11.0数据库构建蛋白互作网络,同时借助Cytoscape 3.8.0软件中Analyze Network插件计算网络中节点的拓扑参数,筛选出网络中起重要作用的蛋白质。将潜在治疗靶点导入RStudio软件,利用clusterProfiler包对潜在治疗靶点进行基因本体论(Gene Ontology, GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)富集分析。最后,借助AutoDock Vina(Vina)平台进行分子对接,预测少腹逐瘀汤主要有效成分与关键靶点的结合度。通过筛选得到少腹逐瘀汤有效成分136个,靶点380个;子宫内膜异位症相关靶点1 627个,痛经相关靶点142个,两者共同作用靶点107个,少腹逐瘀汤治疗子宫内膜异位症痛经的潜在治疗靶点共42个,其中白细胞介素6(IL6)、前列腺素内过氧化物合酶2(PTGS2)等靶点在少腹逐瘀汤干预子宫内膜异位症痛经的生物网络中起到重要作用,主要涉及炎性相关、激素相关信号通路以及丝裂原活化蛋白激酶(MAPK)、磷脂酰肌醇-3激酶(PI3K)-蛋白激酶B(AKT)等可促进细胞增殖的信号转导通路。分子对接结果显示少腹逐瘀汤活性化合物与IL6、PTGS2等关键靶点具有较高结合能力。表明少腹逐瘀汤可通过多靶点、多途径对子宫内膜异位症痛经产生治疗作用,为其治疗子宫内膜异位症痛经的作用机制提供新思路。
Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) were searched for the effective components and targets of Shaofu Zhuyu Decoction. The relevant targets for endometriosis(EMT) and dysmenorrhea were retrieved from the Comparative Toxicogenomics Database(CTD), Therapeutic Target Database(TTD), GeneCards, and DisGeNET with the terms of "endometriosis" and "dysmenorrhea". Cytoscape 3.8.0 was employed to construct the drug-active component-therapeutic target network. A protein-protein interaction(PPI) network was established by STRING 11.0. Analyze Network, the plug-in in the Cytoscape 3.8.0, was used to calculate the topological parameters of the nodes and screen out the critical proteins in the network. The potential therapeutic targets were imported into RStudio and subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses with clusterProfiler package. Finally, the AutoDock Vina(Vina) platform was used for molecular docking to predict the binding degree of the main active components of Shaofu Zhuyu Decoction to key targets. As revealed by the screening results, 136 active components and 380 targets of Shaofu Zhuyu Decoction were obtained. Additionally, there were 1 627 targets related to EMT and 142 targets related to dysmenorrhea with 107 common targets, and 42 potential therapeutic targets of Shaofu Zhuyu Decoction for the treatment of EMT-induced dysmenorrhea. The targets such as interleukin 6(IL6) and prostaglandi-nendoperoxide synthase-2(PTGS2) were pivotal in the biological network of Shaofu Zhuyu Decoction intervention in EMT-induced dysmenorrhea, which involved multiple signaling pathways, including inflammation, hormones, and those promoted cell proliferation [e.g., mitogen-activated protein kinase(MAPK) and phosphatidylinositol-3 kinase(PI3 K)-protein kinase B(AKT)]. The results of molecular docking showed that the active components of Shaofu Zhuyu Decoction had good binding capacities to key targets such as IL6 and PTGS2. The findings of this study demonstrated that Shaofu Zhuyu Decoction could treat EMT-induced dysmenorrhea through multiple targets and multiple pathways, which could provide new ideas for investigating the underlying mechanism of Shaofu Zhuyu Decoction in the treatment of EMT-induced dysmenorrhea.