基于网络药理学和分子对接方法研究右归丸治疗膝骨关节炎的作用机制  

Mechanism of Yougui Pills in the treatment of knee osteoarthritis based on network pharmacology and molecular docking

作　　者：刘小沛 谭从娥[1] 沈霞 王相东 邢文文[1] LIU Xiaopei;TAN Cong’e;SHEN Xia;WANG Xiangdong;XING Wenwen(School of Basic Medical Sciences,Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]陕西中医药大学基础医学院,陕西咸阳712046

出　　处：《西安交通大学学报（医学版）》2022年第3期451-461,共11页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金项目(No.81973754);陕西中医药大学创新团队项目(No.2019-QN06)。

摘　　要：目的采用网络药理学和分子对接的方法探讨右归丸治疗膝骨关节炎(KOA)的作用机制。方法通过检索计算机系统生物学实验室(TCMSP)数据库获取右归丸的活性成分,利用TCMSP、SwissTargetPrediction和TargetNet预测活性成分的靶点,并从中医药整合药理学研究平台(TCMIP)、CTD、DisGeNET和GeneCards数据库检索KOA相关靶点,再与右归丸活性成分靶点取交集,获取右归丸治疗KOA的疗效相关靶点;进而通过DrugBank数据库检索美国食品药品监督管理局(FDA)批准的KOA治疗药物及其靶点,利用Cytoscape构建药物-靶点网络,再以STRING数据库构建蛋白相互作用网络(PPI)并进行网络基因的基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,构建中药-活性成分-关键靶点-显著通路-生物过程网络。结果共获取右归丸组方中9味植物药的活性成分158个,对应490个目标靶点,其中76个靶点为右归丸潜在治疗靶点;在这76个靶点中,有13个与FDA批准的5个治疗KOA的西药的靶点相同;通过蛋白质相互作用(PPI)筛选出18个关键靶点;GO富集分析得到生物学过程1281条、分子功能60条以及细胞组分17条,主要与炎症反应、感染以及氧化应激过程相关;KEGG富集分析得出50条显著富集的通路,主要为IL-17信号通路、肿瘤坏死因子信号通路等,其功能主要涉及免疫系统调控、信号传导、内分泌系统、细胞生长与凋亡等。结论右归丸可以通过多个化合物作用于多个分子靶点发挥其对KOA的治疗作用,其分子机制主要涉及抑制炎症反应、减弱氧化应激和促进软骨细胞增殖等方面。Objective To explore the mechanism of Yougui Pills in the treatment of knee osteoarthritis(KOA)based on network pharmacology and molecular docking.Methods The active components of Yougui Pills were obtained by searching TCMSP database.With the active component targets predicted by TCMSP,SwissTargetPrediction and TargetNet,we searched TCMIP,CTD,DisGeNET and GeneCards databases for KOA related targets.By crossing the two sets of targets,we obtained therapeutic targets of Yougui Pills for KOA.FDA-approved drugs for KOA and their targets were searched in the DrugBank database,and the drug-target network was constructed by using Cytoscape.Then the protein-protein interaction(PPI)network was constructed by using STRING database.After Go and KEGG enrichment analyses,the network of“traditional Chinese Medicine-active components-key targets-significant pathways-biological process”was constructed.Results A total of 132 active components were obtained from the nine herbal medicines of Yougui Pills,corresponding to 490 targets,of which 76 were potential therapeutic targets.Of them 13 were the same as the targets of 5 Western medicines for KOA.We screened out 18 key targets by the PPI network.Go enrichment analysis revealed 1281 biological processes,60 molecular functions,and 17 cellular components,which were mainly related to inflammation,infection and oxidative stress.KEGG enrichment analysis showed that 50 pathways were significantly enriched,including IL-17 signaling pathway and TNF signaling pathway,whose functions were mainly involved in immune system,signal transduction,endocrine system,cell growth and death and other biological processes.Conclusion With multiple compounds acting on multiple molecular targets,Yougui Pills can treat KOA through molecular mechanisms including inhibiting inflammation,reducing oxidative stress,and promoting cartilage cell proliferation.

关 键 词：右归丸 膝骨关节炎(KOA) 网络药理学 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学]