基于网络药理学探讨宫瘤消胶囊治疗子宫肌瘤的作用机制  

Mechanism study of Gongliuxiao capsule in treating uterine myoma based on network pharmacology analysis

作　　者：要慧萍[1] Yao Hui-ping(Department of Obstetrics and Gynecology,The First Hospital of Lanzhou University,Lanzhou 730000,China)

机构地区：[1]兰州大学第一医院妇产科,甘肃兰州730000

出　　处：《兰州大学学报（医学版）》2021年第4期24-29,共6页Journal of Lanzhou University（Medical Sciences）

基　　金：甘肃省科技厅重点研发计划项目(20YF3WA015);甘肃省卫生行业计划项目(GSWSKY2017-51)。

摘　　要：目的筛选宫瘤消胶囊的主要活性成分,探索其治疗子宫肌瘤的主要作用机制。方法利用TCMSP数据库及文献收集查找宫瘤消胶囊主要化学成分;通过ADME生物代谢参数筛选主要活性成分;借助TCMSP、STITCH数据库进行靶点检索;使用TTD、GAD、pharmGkb、Opentarget、DiGSeE在线文本挖掘工具及查阅文献,搜集子宫肌瘤相关靶点;通过Cytoscape软件构建关键成分靶点蛋白相互作用网络,筛选核心靶点;利用Accelrys Discovery Studio 2.5软件进行活性分子与核心靶点对接;利用STRTING数据库分析靶点GO功能富集;运用Cytoscape软件ClueGo插件分析Pathway通路富集。结果筛选宫瘤消胶囊72个潜在活性成分,其对应的靶点171个,子宫肌瘤靶点50个,成分靶点蛋白相互作用核心靶点123个,分子对接表明宫瘤消胶囊潜在活性成分较好地结合到核心靶蛋白的活性口袋中,富集出的核心靶点可靠。GO功能富集分析表明宫瘤消胶囊抗子宫肌瘤主要与细胞代谢、生物过程调节、核染色体、激素受体、转录因子等有关;网络特征富集分析22条生物通路。结论宫瘤消胶囊主要成分核心靶点主要分布于子宫肌瘤密切相关的3条通路中,瘦素、催乳素、Rac1/Pak1/P38/MMP-2信号通路,通过下调信号通路的活性,从而抑制子宫平滑肌瘤细胞的生长或促进细胞凋亡发挥作用。Objective To screen the main active ingredients of the Gongliuxiao capsule and explore its main mechanism of action for the treatment of uterine fibroids.Methods Employing the TCMSP database and literature to find the main chemical components of the Gongliuxiao capsule;using ADME biological meta-bolic parameters to screen active ingredient;applying TCMSP,STITCH database for target search;collecting uterine fibroid related targets by using TTD,GAD database,pharmGkb database,Opentarget database,DiG-SeE online text mining tool and access to literature;using Cytoscape software to build a key component target protein interaction network and screen core targets;docking active molecules with core targets using Accelrys Discovery Studio 2.5 software;applying the STRTING database for target GO function enrichment analysis;utilizing Cytoscape software ClueGo plugin for pathway enrichment analysis.Results 72 potential active ingredients of the Gongliuxiao capsule were screened,which corresponded to 171 targets;50 uterine fibroids targets and 123 core target protein interaction core targets were obtained.Molecular docking showed that the potential active ingredients of the Gongliuxiao capsule were better bound to the active pocket of the core target protein,and the enriched core target was reliable.The GO functional enrichment analysis showed that the effect of the Gongliuxiao capsule on anti-uterine fibroids was mainly related to cell metabolism,regulation of biological processes,nuclear chromosomes,hormone receptors,transcription factors,etc.;22 biological pathways were obtained through a network feature enrichment analysis.Conclusion The core targets of the Gongliuxiao capsule are mainly distributed in 3 pathways closely related to uterine fibroids,leptin,prolactin,Rac1/Pak1/P38/MMP-2 signaling pathway via down-regulating the activity of the signaling pathway,thereby inhibiting the uterine leiomyoma cell growth or promoting cell apoptosis.

关 键 词：宫瘤消胶囊 子宫肌瘤 网络药理学 核心靶点 信号通路 

分 类 号：R593.22[医药卫生—内科学]