牛膝治疗骨关节炎作用机制的网络药理学探讨  

Study on Mechanism of Niuxi(Achyranthis bidentatae Radix) in Treatment of Osteoarthritis Based on Network Pharmacology

作　　者：魏锦强 孙赫[2] 曹学伟[2] 徐逸生[2] 李春花 吴柯柯 WEI Jinjiang;SUN He;CAO Xuewei;XU Yisheng;LI Chunhua;WU Keke(Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China;Guangdong Province Hospital of Chinese Medicine,Guangzhou 510120 Guangdong,China)

机构地区：[1]广州中医药大学,广东广州510006 [2]广东省中医院,广东广州510120

出　　处：《中药新药与临床药理》2020年第9期1052-1060,共9页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省中医院与香港中文大学医学院生物医学学院基础临床协同创新计划项目(YN2018HK04);广东省中医院院内专项(2017KT1334)。

摘　　要：目的采用网络药理学的原理和方法探讨牛膝治疗骨关节炎(osteoarthritis,OA)的物质基础和作用机制。方法先通过TCMSP、Batman-TCM、DrugBank数据库及手工检索获得牛膝活性成分及作用靶点,然后与从Drugbank等6个数据库挖掘的骨关节炎疾病靶点匹配,经Cytoscape软件构建网络、拓扑学分析,再分别用ClueGO和R软件包clusterProfiler对关键靶点进行GO功能和KEGG通路富集分析,最后采用AutoDock 4.2和PyRx软件对活性成分和主要核心靶点进行分子对接。结果获得22个牛膝潜在活性成分和203个靶蛋白,收集到205个骨关节炎疾病靶点,得到29个牛膝治疗骨关节炎的关键靶点。GO功能和KEGG通路富集结果显示,牛膝治疗骨关节炎涉及趋化因子代谢、吞噬作用调节等多个生物过程,以及涉及软骨细胞增殖、分化、凋亡及炎症反应等多条通路。分子对接结果提示牛膝治疗骨关节炎的活性成分与核心靶点IL6、PTGS2、VEGFA、TNF、TP53有良好的亲和力。结论牛膝治疗骨关节炎具有多靶点、多通路的特点。牛膝可能通过多条通路直接或者间接影响骨关节炎的发生和发展,与目前牛膝治疗骨关节炎的机制研究相符。Objective To predict the active ingredient through screening the chemical ingredients of Niuxi(Achyranthis bidentatae radix) by means of network pharmacology,and to expound the material basis and mechanism underlying the treatment of osteoarthritis.Methods First,the main active ingredients of Achyranthis bidentatae radix were predicted and the relevant targets about osteoarthritis were collected using TCMSP,BatmanTCM,DrugBank and manual retrieval,and then matched with the targets of osteoarthritis retrieved from 6 databases including Drugbank.The "active ingredient-target" and "target-related diseases" network were constructed by the Cytoscape software.Finally,the main targets and related pathways were analyzed by GlueGO and KEGG plugin using ClueGO and ClusterProfiler.AutoDock 4.2 and PyRx were used for the docking between the core components and targets.Results A total of 22 potential active ingredients and 203 targets were obtained from Achyranthis bidentatae radix.A total of 205 targets related to osteoarthritis were screened from Drugbank.A total of 29 key targets related to the development of osteoarthritis were retrieved from the network.The analysis of GlueGO and KEGG showed that the herb involved not only the biological functions of the metabolism of chemokine and the regulation of phagocytosis,but also the proliferation,differentiation and apoptosis of chondrocyte and inflammatory response.Results of molecular docking showed that core components for the treatment of OA in Achyranthis bidentatae radix had good affinity with the core targets IL6,PTGS2,VEGFA,TNF,and TP53.Conclusion This study reveals that Achyranthis bidentatae radix not only has multi-active ingredients,but also has multi-targets and multi-pathways for OA.It may directly or indirectly affect the occurrence or development of OA,which was in line with the current research on the mechanisms.

关 键 词：骨关节炎 牛膝 网络药理学 作用机制 信号通路 分子对接 

分 类 号：R285.5[医药卫生—中药学]