基于网络药理学探讨黄芪治疗骨质疏松症的分子机制

Exploring the molecular mechanism of Astragalus in the treatment of osteoporosis based on network pharmacology

目的基于网络药理学方法探讨黄芪治疗骨质疏松症的潜在作用机制。方法通过TCMSP数据库进行黄芪潜在化学成分获取和靶点预测,运用GeneCards及OMIM数据库预测筛选与骨质疏松症相关的基因,采用R软件进行药物靶点与疾病靶点映射匹配。通过Cytoscape软件进行药物-成分-靶点-疾病可视化网络建立,借助String数据库在线平台进行蛋白互作网络构建,采用DAVID数据库进行生物过程及通路注释。结果通过筛选共得到黄芪主要化合物20种,药物靶点218个,与骨质疏松症相关的靶点22个,主要影响转录因子活性、配受体活性、细胞因子活性、类固醇激素受体活性等生物过程,涉及类风湿关节炎通路、破骨细胞分化通路、IL-17因子通路、AGE-RAGE信号通路、雌激素通路等。结论研究结果证实黄芪具有多成分、多靶点、多过程的作用特征,不仅直接参与骨代谢,还间接通过消化系统、循环系统、内分泌系统等影响骨微环境,调节骨代谢,治疗骨质疏松症;Toll样受体信号通路、炎症性肠病、PI3K-Akt信号通路等与消化系统、脾脏相关通路的富集,可能是黄芪从脾治疗骨质疏松症的重要证据。

Objective To explore the potential mechanism of Astragalus treatment of osteoporosis based on network pharmacology.Methods The potential chemical components and target prediction of Astragalus were obtained in TCMSP database.GeneCards and OMIM database were used to predict and screen osteoporosis-related genes,and R software was used to match drug targets with disease targets.The drug-component-target-disease visualization network was established by Cytoscape.The Protein Interaction Network was constructed by using the String database online platform.The DAVID database was used for biological process and pathway analysis.Results A total of 20 major ingredients of Astragalus were obtained after screening,and 218 targets were predicted.22 targets related to osteoporosis,mainly affecting transcription factor activity,ligand activity,cytokine activity,steroid hormone receptor activity,etc and involved in rheumatoid arthritis pathway,osteoclast differentiation pathway,IL-17 factor pathway,AGE-RAGE signaling pathway,estrogen pathway,etc.Conclusion The result of this study confirmed that Astragalus has multiple components,multiple targets,and multiple processes.It is preliminarily stated that it is not only directly involved in bone metabolism,but also indirectly through the digestive system,circulatory system,endocrine system and other systems regulates environmental of bone metabolism in the treatment of osteoporosis;The enrichment of the Toll-like receptor signaling pathway,inflammatory bowel disease,PI3K-Akt signaling pathway and other related pathways of the digestive system and spleen may be important evidence for the treatment of osteoporosis from the spleen.