基于网络药理学和分子对接技术探究骨疏灵治疗骨质疏松的有效成分及作用机制  

Based on Network Pharmacology and Molecular Docking Technology to Explore the Effective Ingredients and Mechanism of Gushuling in Treatment of Osteoporosis

作　　者：桑冉[1] 常红 王雷 方朝晖[3] 陈卫东 张彩云 SANG Ran;CHANG Hong;WANG Lei;FANG Chao-hui;CHEN Wei-dong;ZHANG Cai-yun(Department of Pharmacy,First Affiliated Hospital of Bengbu Medical College,Bengbu Anhui 233004;School of Pharmacy,Anhui University of Chinese Medicine,Hefei Anhui 230012;Department of Endocrinology,The First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei Anhui 230031)

机构地区：[1]蚌埠医学院第一附属医院药剂科,安徽蚌埠233004 [2]安徽中医药大学药学院,安徽合肥230012 [3]安徽中医药大学第一附属医院内分泌科,安徽合肥230031

出　　处：《世界中西医结合杂志》2021年第11期2041-2050,共10页World Journal of Integrated Traditional and Western Medicine

基　　金：安徽高校自然科学研究重点项目(KJ2019A0314)。

摘　　要：目的利用网络药理学和分子对接技术探究由淫羊藿、牛膝、黄芪、牡蛎组成的骨疏灵治疗骨质疏松(Osteoporosis,OP)的有效成分及作用机制,为新药研发及院内复方制剂临床推广运用提供参考。方法通过TCMSP、中药与化学成分数据库获取淫羊藿、牛膝、黄芪、牡蛎的主要化学成分及其靶点,根据ADME属性筛选各中药活性成分;基于OMIM、DrugBank、TTD及GeneCards数据库获取骨质疏松的主要靶点;借助STRING平台进行蛋白质相互作用分析,构建PPI网络并结合Cytoscape 3.7.1软件构建核心PPI网络;采用Metascape平台分析“药物-成分-靶点”及其参与的生物过程及通路,之后使用Cytoscape 3.7.1软件构建“骨疏灵成分-骨质疏松靶点-通路”网络,最后通过Autodock软件对关键成分和关键靶点进行分子对接验证。结果骨疏灵治疗骨质疏松的核心活性成分为槲皮素、山柰酚、木樨草素等,核心靶点有PTGS2、JUN、TNF等,分子对接结果亦验证大部分靶点与成分的结合活性较好。骨疏灵治疗骨质疏松主要涉及破骨细胞分化、内分泌抵抗、PI3K-Akt、HIF-1和MAPK等信号通路。结论本研究初步揭示了骨疏灵通过多成分-多靶点-多通路治疗骨质疏松的作用机制,为骨疏灵的临床推广使用提供理论基础。Objective Using network pharmacology and molecular docking technology to explore the effective ingredients and mechanism of action of Gushuling composed of Yinyanghuo,Niuxi,Huangqi,and Muli in the treatment of osteoporosis,and provide for the development of new drugs and the clinical application of compound preparations in the hospital reference.Methods The main chemical components and targets of Yinyanghuo,Niuxi,Huangqi,and Muli were obtained through TCMSP,Chinese medicine and chemical component database,and the active components of each Chinese medicine were screened according to ADME attributes.Bone quality was obtained based on OMIM,DrugBank,TTD and GeneCards databases.The main target of looseness.The STRING platform was used to analyze protein interactions,built a PPI network and combined with Cytoscape 3.7.1 software to build a core PPI network.The Metascape platform was used to analyze“drug-component-target”and its participating biological processes and pathways.Afterwards,Cytoscape 3.7.1 software was used to construct the“Gushuling component-osteoporosis target-pathway”network,and finally the key components and key targets were verified by molecular docking through Autodock software.Results The core active ingredients of Gushuling in the treatment of osteoporosis are quercetin,kaempferol,luteolin,etc.The core targets are PTGS2,JUN,TNF,etc.,and the molecular docking results also verify that most of the targets and ingredients are effective.The binding activity is better.Gushuling treatment of osteoporosis mainly involves signal pathways such as osteoclast differentiation,endocrine resistance,PI3K-Akt,HIF-1 and MAPK.Conclusions This study preliminarily revealed the mechanism of Gushuling in the treatment of osteoporosis through multiple components,multiple targets and multiple pathways,and provided a theoretical basis for the clinical application of Gushuling.

关 键 词：骨疏灵 网络药理学 骨质疏松 分子对接 

分 类 号：R285.6[医药卫生—中药学]