基于入血成分和网络药理学研究桂枝茯苓胶囊抗乳腺增生症的作用机制

Mechanism of Guizhi Fuling Capsule constituents migrating to blood in the treatment of mammary gland hyperplasia by network pharmacology

目的利用网络药理学方法,研究桂枝茯苓胶囊入血成分治疗乳腺增生症的作用机制。方法运用PharmMapper、Gene Cards、PubMed、Gen CLip 3及STRING平台,筛选入血成分抗乳腺增生症靶点,构建靶蛋白相互作用(PPI)网络并导入Cyto NCA插件,计算PPI网络的重要拓扑参数筛选关键靶点;利用Clue GO插件进行关键靶点GO生物过程分析;通过DAVID数据库进行关键靶点KEGG通路富集。结果桂枝茯苓胶囊12种入血成分作用于197个乳腺增生症靶点,其中包括转录及凋亡蛋白AKT1、MAPK1、CASP3、MAPK8、BCL2L1、MDM2、STAT1;信号传导蛋白SRC、HRAS、HSP90AA1、MAPK14、PIK3R1、MAP2K1、PTPN11等;血管生成蛋白EGFR、MMP2、KDR、NOS3等;激素相关受体IGF1、ESR1、AR、IGF1R;炎症因子IL2;氧化还原酶CAT等。参与肌醇脂质介导的信号转导、乳腺上皮细胞发育、细胞对活性氧的反应、一氧化氮合酶生物合成过程的正调控、T细胞共刺激、VEGF受体信号通路等14大类生物过程,调节雌激素、催乳素、凋亡、PI3K-Akt、VEGF、T细胞受体、TNF、MAPK等信号通路。结论桂枝茯苓胶囊主要通过恢复性激素平衡、促进乳腺细胞凋亡,以及抗炎、抗氧化、抗血管生成等药理作用来治疗乳腺增生症。

Objective To study the mechanism of Guizhi Fuling Capsule treating in mammary gland hyperplasia by network pharmacology.Methods Using PharmMapper,GeneCards,PubMed,GenCLip 3,and STRING platform to screen mammary gland hyperplasia targets of constituents migrating to blood,we constructed a protein-protein interaction(PPI)network.These targets were imported into the CytoNCA plug-in to calculate the important topological parameters of the PPI network to screen key targets.The ClueGO plug-in was used to analyze the biological process of these key targets,and the DAVID database was used to analyze KEGG pathway enrichment.Results Twelve constituents of constituents migrating to blood of Guizhi Fuling Capsule acted on 197 targets in mammary gland hyperplasia,which included 31 key targets,such as transcriptional and apoptotic proteins AKT1,MAPK1,CASP3,MAPK8,BCL2L1,MDM2,and STAT1,signal transduction proteins SRC,HRAS,HSP90AA1,MAPK14,PIK3R1,MAP2K1,and PTPN11,angiogenesis-related targets EGFR,MMP2,KDR,and NOS3,hormone-related receptors IGF1,ESR1,AR,and IGF1R,inflammatory factor IL2,and oxidoreductase CAT.These targets were enriched in 14 different biological processes,including inositol lipid-mediated signaling,mammary gland epithelium development,cellular response to reactive oxygen species,positive regulation of nitric-oxide synthase biosynthesis,T cell co-stimulation,and VEGF receptor signaling pathway,and regulate signaling pathways such as estrogen,prolactin,apoptosis,PI3K-Akt,VEGF,T cell receptors,TNF,and MAPK.Conclusions Guizhi Fuling Capsule is mainly used for the treatment of mammary gland hyperplasia by restoring the balance of sex hormones and promoting the apoptosis of mammary gland cells,as well as having anti-inflammatory,anti-oxidation,anti-angiogenesis,and other pharmacological effects.