当归-骨碎补配伍治疗骨折三期辨证中期的网络药理学机制

Network Pharmacological Mechanism of Compatibility of Radix Angelicae Sinensis-Rhizoma Drynariae for Mid-Stage Fracture in Three Treatment Stages

【目的】通过网络药理学探讨当归-骨碎补配伍治疗骨折三期辨证中期的作用机制。【方法】借助中药系统药理学分析平台(TCMSP)筛选出当归、骨碎补的有效化合物及其靶点,通过STRING、CTD及GeneCards数据库对当归-骨碎补治疗闭合骨折的靶点进行数据分析,利用Cytoscape 3.7.1开放源码的生物信息分析软件构建化合物-靶点网络、蛋白-蛋白互作网络、化合物-靶点-疾病网络。应用ClueGO插件对当归-骨碎补治疗闭合骨折的靶点进行基因本体论(GO)分析,并对核心靶点基因进行京都基因与基因组百科全书(KEGG)通路富集分析。【结果】共筛选出当归、骨碎补有效化合物20个,闭合骨折核心靶点25个,当归-骨碎补治疗闭合骨折的KEGG富集通路共51条,包括低氧诱导因子1(HIF-1)信号通路、肿瘤坏死因子(TNF)信号通路、磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/Akt)信号通路、血管内皮生长因子(VEGF)信号通路等。【结论】当归-骨碎补配伍可能通过主要活性成分β-谷甾醇、山柰酚、柚皮素、木犀草素、黄烷酮类、固醇类、海州骨碎补苷等,作用于HIF-1、TNF、PI3K/Akt、VEGF等信号通路促进骨折三期辨证中期的愈合。

Objective To explore the mechanism of compatibility of Radix Angelicae Sinensis-Rhizoma Drynariae for mid-stage fracture in the treatment three stages based on network pharmacology. Methods The effective constituents of Radix Angelicae Sinensis-Rhizoma Drynariae and their targets were screened from Traditional Chinese Medicines Systems Pharmacology Platform(TCMSP) database, and the targets of Radix Angelicae Sinensis-Rhizoma Drynariae for fracture were analyzed by STRING,CTD and GeneCards databases,and then a Cytoscape 3.7.1 open source bioinformation analysis software was used to construct the constituent-target network,protein-protein interaction network and constituent-target-disease network. Finally,ontology(GO)analysis of the targets of Radix Angelicae Sinensis-Rhizoma Drynariae for closed fracture was carried out by ClueGO plug-in,and then Kyoto encyclopedia of genes and gnomes(KEGG)enrich analysis of core target genes were performed.Results We screened out 20 effective constitutes from Radix Angelicae Sinensis and Rhizoma Drynariae,25 fracture core targets for closed fracture,and 51 KEGG enrichment pathways including hypoxia-inducible factor 1(HIF-1)signaling pathway, tumor necrosis factor(TNF) signaling pathway, phosphatidyl inositol-3-kinase/protein kinase B(PI3 K/Akt)signaling pathway and vascular endothelial growth factor(VEGF)signaling pathway,etc. on Radix Angelicae Sinensis-Rhizoma Drynariae for closed fracture. Conclusion Compatibility of Radix Angelicae Sinensis-Rhizoma Drynariae promotes healing of mid-stage fracture in the treatment three stages possible through HIF-1,TNF,PI3 K/Akt,VEGF,etc. signaling pathways with main active constituent beta-sitosterol,kaempferol,naringenin,luteolin,flavanones,stigmasterols,marioside_qt,and so on.