乳腺宁治疗急性乳腺炎的网络药理学研究

Network pharmacological analysis of Ruxianning in the treatment of acute mastitis

目的:分析乳腺宁搽剂对急性乳腺炎的药效物质基础及其靶点的作用机制。方法:通过查询TCMSP、CNKI等相关数据库,筛选出乳腺宁组方药物木芙蓉和穿心莲的潜在化学活性物质,通过SWISS TARGET预测相关靶点蛋白,采用疾病数据库OMIM、Gene cards预测炎症的作用靶点,并获取药物与疾病交集靶点,通过Cytoscape(3.7.2)软件,构建“活性成分与疾病靶点”的可视化网络图。通过String数据库平台构建蛋白互作网络,再利用David平台和R语言进行GO富集分析和KEGG富集分析。结果:经数据库筛选出乳腺宁主要活性成分35个,其中关键化学成分为5-羟基-7,8,2'-三甲氧基黄酮(Andrographin)和新穿心莲内酯(3-[2-[(1R,4aS,5R,8aS)-5,8a-dimethyl-2-methylene-5-methylol-decalin-1-yl]ethyl]-5H-furan-2-one),乳腺宁与急性乳腺炎的共同靶点共32个,获得ALB、EGFR、AKT1、IL1B、MPO等17个核心基因;获得140条GO生物学过程包括血管收缩调节、氧化应激反应、炎症反应、脂氧合酶途径、蛋白质磷酸化的正调控等,26条KEGG相关信号通路,涉及癌症信号通路、急性髓系白血病、NF-κB信号通路等。结论:乳腺宁搽剂治疗急性乳腺炎具有多成分、多靶点、多通路的特点;乳腺宁搽剂中的穿心莲黄酮等主要活性成分基于NF-κB等信号通路调控机体炎症反应而发挥治疗急性乳腺炎的作用。

In this study we analyzed the active ingredients and mechanism of action of Ruxianning on acute mastitis.The potential chemical active substances in Ruxianning were screened out by searching TCMSP and CNKI databases,and the related target proteins were predicted by using SWISS TARGET.The action targets of acute mastitis were predicted by using OMIM and Gene cards databases,and the intersection targets of the drug and the disease were obtained to build a visualization network of active ingredients and disease targets by using Cytoscape(3.7.2)software.The protein interaction network was constructed by String database platform,and then GO enrichment analysis and KEGG enrichment analysis were carried out using David platform and R language.A total of 35 active ingredients were screened out from the databases,and the key chemical components were 5-hydroxy-7,8,2'-trimethoxyflavone(andrographin)and (3-[2-[(1R,4As,5R,8As)-5,8a-dimethyl-2-methylene-5-methyl-decalin-1-yl]ethyl]-5h-furan-2-one).There were 32 common targets of Ruxianning and acute mastitis.17 PPI core genes were obtained,including ALB,EGFR,AKT1,IL1B,MPO,etc.140 GO biological processes were obtained,including vasoconstriction regulation,oxidative stress response,inflammatory response,lipoxygenase pathway,positive regulation of protein phosphorylation,etc.26 KEGG related signal pathways were obtained,involving cancer signaling pathway,acute myeloid leukemia,NF-κB signaling pathway,etc.Based on network pharmacology,we explored the active ingredients and mechanism of Ruxianing in the treatment of acute mastitis,and provided reference for the development of new externally applied agent for acute mastitis.