淫羊藿治疗股骨头坏死的分子机制分析

目的:基于网络药理学和生物信息学研究淫羊藿治疗股骨头坏死可能的分子机制。方法:通过中药系统药理学数据库和分析平台对淫羊藿可能的活性成分和靶点进行筛选和预测,针对TTD,Drug Bank,OMIM,GAD,Pharm GKB等数据库与股骨头坏死相关的作用靶点进行挖掘,结合生物信息学手段,明确淫羊藿防治股骨头坏死的特异性靶点,采用Clue GO进行信号通路富集分析,以进一步分析其可能的分子机制。结果:在中药系统药理学数据库和分析平台中共检索出与淫羊藿相关成分130个,根据口服生物利用度(OB)和药物相似性(DL)参数筛选获得入血活性成分23个,利用相关靶点预测技术预测可能的靶点102个;通过上述疾病基因相关数据库共检索到与股骨头坏死发生,发展密切相关的已知靶点72个。利用Cytoscape软件构建活性成分及疾病的蛋白质-蛋白质相互作用关系网络图,合并网络图并行拓扑分析筛选出关键基因135个;采用Clue GO信号通路富集分析显示,淫羊藿作用于股骨头坏死的关键节点涉及的信号通路主要被富集在细胞增殖、细胞凋亡、炎症、应激及癌症相关等80条信号通路。结论:淫羊藿治疗股骨头坏死具有多成分,多靶点的特点;其主要通路不仅直接参与骨重建的细胞增殖、凋亡及分化,调节成骨、破骨代谢平衡,还通过调节免疫、炎症及应激反应等干预和影响骨微环境以达到控制疾病发生发展的目的,与目前治疗股骨头坏死的作用机制相符合。

Molecular Mechanism of Epimedii Folium in Treating Osteonecrosis of Femeral Head

Objective: To investigate the potential molecular mechanism of Epimedii Folium in the treatment of osteonecrosis of femeral head based on the network pharmacology and bioinformatics. Method: The method of network pharmacology was used to determine and screen out the potential compounds of Epimedii Folium through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and predict the drug-related gene/protein targets by means of such databases as TTD and DrugBank, OMIM, GAD and PharmGKB. Bioinformatic method was used to determine the specific target of Epimedii Folium in prevention and treatment of osteonecrosis of femeral head. ClueGO was applied in the signal pathway enrichment analysis to further analyze the molecular mechanism of Epimedii Folium in treatment of osteonecrosis of femeral head. Result: The 130 compounds related to Epimedii Folium were retrieved in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. According to the parameters of oral bioavailability (OB) and drug-likeness (DL), a total of 23 blood transfusion components were screened out, and 102 targets were predicted by using the relevant target prediction technique. A total of 72 known targets closely related to the development of osteonecrosis of femeral head were retrieved in the disease-related databases. Cytoscape software was used to construct and synthesize the protein-protein interaction network of active ingredients and diseases, and 135 key genes were screened out by the network topological analysis. ClueGO analysis showed that the key signaling pathways involving the effect of Epimedii Folium on osteonecrosis of femeral head were mainly enriched in 80 signaling pathways, such as cell proliferation, apoptosis, inflammation, stress and cancer related signaling pathways. Conclusion: Epimedii Folium has the characteristics of multiple targets and multicomponents in the treatment of osteonecrosis of femeral head. Its main pathways not only directly participate in the cell proliferation, apoptosis and differentiation and the regulation of the balance of osteogenesis and osteoclasts, but also interfere and affect the bone microenvironment by regulating immunity, inflammation and stress, so as to control the occurrence and development of diseases. This is consistent with the current mechanism in treating the osteonecrosis of femeral head.