补肾活血汤促进骨质疏松性骨折愈合的主要活性成分及网络药理机制研究

Study on the Main Active Components and Network Pharmacological Mechanism of Bushen Huoxue Decoction in Promoting Osteoporotic Fracture Healing

【目的】利用网络药理学方法探讨补肾活血汤治疗骨质疏松性骨折的主要活性成分及药理作用机制。【方法】从中药系统药理学数据库与分析平台(TCMSP)中收集补肾活血汤的化学成分。通过DisGeNET数据库收集骨质疏松症的疾病靶点。通过韦恩图筛选出补肾活血汤治疗骨质疏松症的预测作用靶点。通过基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析获得补肾活血汤治疗骨质疏松性骨折的生物过程和信号通路。采用Cytoscape 3.9.1软件构建“中药成分-疾病靶点-通路”网络图,并通过拓扑参数分析,以度值作为考察,获得补肾活血汤治疗骨质疏松性骨折的主要活性成分。通过在线String 11.5软件构建蛋白-蛋白相互作用(PPI)网络,并通过拓扑参数分析补肾活血汤治疗骨质疏松性骨折在蛋白分子水平上的药理机制。【结果】共筛选出1 236个化学成分,其中包含了72个预测作用靶点,涉及DNA的转录、翻译甚至酶与酶之间的结合等生物过程,与糖尿病、动脉粥样硬化、癌症等KEGG信号通路有交集。【结论】补肾活血汤主要是通过脱氢二甘醇4、Yangambin、阿托品、花生四烯酸、鞣花酸、豆甾醇、异鼠李素等主要成分调控核转录因子p65、丝裂原活化蛋白激酶、雌激素受体、肿瘤坏死因子、细胞肿瘤抗原等蛋白分子发挥促进骨质疏松性骨折愈合的作用。

Objective To investigate the main active components and pharmacological mechanism of Bushen Huoxue Decoction in the treatment of osteoporotic fractures by network pharmacology.Methods The chemical constituents of Bushen Huoxue Decoction were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The disease targets of osteoporosis were collected through the DisGeNET database.The predictive targets of Bushen Huoxue Decoction in the treatment of osteoporosis were screened by Venn diagram.Through gene ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis,the biological processes and signaling pathways of Bushen Huoxue Decoction in the treatment of osteoporotic fractures were preliminarily obtained.Cytoscape 3.9.1 software was used to construct the network diagram of Chinese medicinal components-disease targets-pathways.Through the analysis of topological parameters and the degree value as the investigation,the main active components of Bushen Huoxue Decoction in the treatment of osteoporotic fractures were obtained.The protein-protein interaction(PPI) network was constructed by online String 11.5 software,and the pharmacological mechanism of Bushen Huoxue Decoction in the treatment of osteoporotic fractures at the protein molecular level was obtained by topological parameter analysis.Results A total of 1 236 chemical components were screened out,including 72 predicted targets.It involves biological processes such as DNA transcription,translation,and even binding between enzymes,and intersects with KEGG signaling pathways such as diabetes,atherosclerosis and cancer.Conclusion Bushen Huoxue Decoction mainly through dehydrodiethylene glycol 4,Yangambin,Atropine,arachidonic acid,ellagic acid,stigmasterol,isorhamnetin and other major components acting on nuclear transcription factor p65,mitogenactivated protein kinase,estrogen receptor,tumor necrosis factor,cell tumor antigen and other protein molecules play a role in the promotion of osteoporotic fractures healing.