目的:研究恒古骨伤愈合剂(Osteoking)治疗股骨头坏死(osteonecrosis of the femoral head,ONFH)的有效成分、作用靶点及作用机制.方法:通过TCMSP数据库,挖掘Osteoking的主要成分和作用靶点;通过GEO、DisGeNET、GeneCards等数据库获取ONFH疾病相关基因.利用Venny 2.1.0在线工具将主要成分作用靶点和疾病靶点取交集,通过DAVID在线工具对交集基因进行蛋白质组学基因结构功能通路分析;使用Cytoscape 3.9.1软件构建药物成分-化合物-靶点相互作用图,并利用 STRING 网络平台制作蛋白互作网络(protein-protein interaction networks,PPI).运用R语言软件包,开展GO功能及 KEGG通路的富集分析.结果:筛选得到Osteoking 17个主要活性成分和75个作用靶点,主要活性成分包括常春藤苷、豆甾醇等;作用靶点包括雌激素受体(ESR1)、凝血因子(F3)等.Osteoking通过调控机体代谢、雌激素受体/配体等信号通路改善ONFH;Osteoking主要活性成分与靶点进行分子对接后的结合能均小于-5 kJ/mol,具有较好的结合活性.结论:Osteoking能够通过修复ONFH坏死组织血管,改善骨组织血运障碍,提高成骨细胞的分化能力,从而治疗ONFH,为进一步研究Osteoking治疗ONFH的作用机制提供线索.
Exploration of the mechanism of Osteoking in the treatment of osteonecrosis of the femoral head based on network pharmacology
Objective:To study the effective components,targets of action and mechanism of Osteoking in the treat-ment of osteonecrosis of the femoral head(ONFH).Methods:The main components and targets of action of Osteoking were obtained through TCMSP database.ONFH disease-related genes were obtained from GEO,DisGeNET,GeneCards and other databases.The online tool Venny 2.1.0 was used to take the intersection of the main component action targets and dis-ease targets.The DAVID online tool was used to analyze the gene structure and function pathway of the intersection genes by proteomics.Cytoscape 3.9.1 software was used to construct drug component-compound-target interaction maps,and STRING network platform was used to generate protein-protein interaction networks(PPI).The enrichment analysis of GO function and KEGG pathway was performed by using R language software package.Results:17 main active components and 75 action targets of Osteoking were obtained.The main active components included hederin,stigmasterol,etc.The targets of action included estrogen receptor(ESR1),blood coagulation factor(F3),etc.Osteoking could improve ONFH by regu-lating metabolism,estrogen receptor/ligand and other signaling pathways.The binding energy of Osteoking was lower than-5 kJ/mol after molecular docking between the main effective components and the targets,so Osteoking had good binding activity.Conclusion:Osteoking can treat ONFH by repairing the necrotic tissue blood vessels of ONFH,improving the blood supply disorder of bone tissue,and improving the differentiation ability of osteoblasts,thus providing clues for further research on the mechanism of Osteoking in the treatment of ONFH.
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