基于网络药理学及生物信息学研究骨碎补-淫羊藿治疗骨质疏松的作用机制

Study on the mechanism of the drynariae rhizoma-epimedii folium in the treatment of osteoporosis based on network pharmacology and bioinformatics

目的基于网络药理学和生物信息学探讨“骨碎补-淫羊藿”治疗骨质疏松的分子机制,为骨质疏松治疗提供新的靶点。方法通过TCMSP数据库筛选“骨碎补-淫羊藿”的活性成分,联合UniProt数据库预测其调控靶点,并根据GEO数据库预测治疗骨质疏松的靶点。借助R语言获取治疗骨质疏松的有效靶点,并构建“药物-成分-靶点-通路”网络。利用Cytoscape软件构建蛋白互作网络,并对关键活性成分与关键靶点之间进行分子对接验证,利用DAVID数据库对交集基因进行GO和KEGG分析。结果得到活性成分39个,治疗靶点17个。蛋白互作网络中的核心靶点主要有ESR1、PRKDC、HSPA8、EP300和HSP90AA1。DAVID富集分析主要涵盖异源代谢、固醇代谢及破骨细胞分化调控等生物学过程,涉及MAPK、NF-κB、PI3K-AKT及HIF-1等信号通路。结论通过网络药理学和生物信息学对“骨碎补-淫羊藿”治疗骨质疏松的分析不仅能识别目前已知的相关生物学过程和信号通路,还可为进一步研究“骨碎补-淫羊藿”治疗骨质疏松的药效物质基础及作用靶点提供参考。

Objective Based on network pharmacology and bioinformatics,the molecular mechanism of drynariae rhizoma-epimedii folium in the treatment of osteoporosis was discussed,in order to provide a new target for the treatment of osteoporosis.Methods The active ingredients of drynariae rhizoma-epimedii folium were screened through TCMSP database.The regulatory target was predicted through the UniProt database.The target for the treatment of osteoporosis was predicted according to the GEO database.The effective targets for the treatment of osteoporosis were obtained and the drug-component-target-pathway network was established using R language.The protein interaction network was constructed and the molecular docking between key active ingredients and key targets was verified using the Cytoscape software.Finally,the GO analysis and the KEGG pathway analysis of intersection genes were performed by using the DAVID database.Results Thirty-nine active ingredients and 17 therapeutic targets were obtained.The core targets in the protein interaction network were ESR1,PRKDC,HSPA8,EP300,and HSP90AA1.DAVID enrichment analysis showed that the biological process mainly covered xenobiotic metabolic process,steroid metabolic process,regulation of osteoclast differentiation.Signal pathway mainly included NF-κB signaling pathway,PI3K-AKT signaling pathway,and HIF-1 signaling pathway.Conclusion Analysis of the treatment of osteoporosis with drynariae rhizoma-epimedii folium through pharmacology and bioinformatics network enables us not only to identify the currently known biological processes and signaling pathways,but also to provide a reference for further research on the substance basis and action targets of drynariae rhizoma-epimedii folium in the treatment of osteoporosis.