基于网络药理学与分子对接技术探讨补肾活血方治疗多发性骨髓瘤的物质基础与作用机制

Exploration on material basis and mechanism of Bushen Huoxue Decoction in treating multiple myeloma based on network pharmacology and molecular docking technology

目的运用网络药理学与分子对接技术探寻补肾活血方治疗多发性骨髓瘤(MM)的活性成分、靶点及信号通路。方法在中药系统药理学数据库与分析平台检索补肾活血方所含中药成分;运用Swiss Target Prediction数据库预测补肾活血方药物的活性成分对应的靶点基因。在GEO数据库中以“multiple myeloma”为关键词检索出同时含有MM患者和正常人骨髓样本的人源基因芯片,并采用GEO2R在线分析工具筛选差异表达基因。采用DAVID数据库对交集基因进行基因本体及京都基因和基因组数据库(KEGG)分析。进一步使用Cytoscape软件分析网络拓扑参数,根据度值、接近中心性、介数筛选出核心基因与关键成分;最后使用AutoDock Vina对核心基因与关键成分进行分子对接验证。结果补肾活血方有效活性成分97个,治疗MM的潜在靶基因98个,交集基因构建的“活性成分-靶点”网络共包含节点195个、边756条。KEGG通路主要涉及癌症信号通路、MAPK信号通路、NF-κB信号传导通路、破骨细胞分化通路、TNF信号通路等。分子对接显示补肾活血方关键成分与MM关键靶点均能自发结合,其中甲基升麻苷与MAPK14结合性能最佳。结论补肾活血方通过多组分、多靶点、多通路发挥抑制MM细胞增殖、增强化疗效果、减轻骨破坏等作用,对MM的治疗具有一定的价值。

Objective To explore the effective components and pharmacological targets,signal pathways of Bushen Huoxue Decoction in treating multiple myeloma based on network pharmacology and molecular docking technology.Methods The chemical components of Bushen Huoxue Decoction were searched in traditional Chinese medicine systems pharmacology database and analysis platform.The whole target genes corresponding with the components of Bushen Huoxue Decoction were predicted by searching Swiss Target Prediction database.The gene microarray data of multiple myeloma patients and healthy persons were retrieved from the GEO database by taking“multiple myeloma”as the keyword and compared to screen the differentially expressed genes by the internet analyzer of GEO2R.DAVID database was used for gene ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of intersection genes.Further,Cytoscape software was used to analyze the network topology parameters,and the core genes and key components were selected according to the degree value,proximity to centrality and intermediary number.Finally,AutoDock Vina was used to verify the molecular docking between core genes and key genes.Results About 97 active components and 98 potential target genes were collected for Bushen Huoxue Decoction corresponding with multiple myeloma therapy.Active ingredients-target network constructed by intersection genes contained 195 nodes and 756 edges.KEGG pathway mainly involved cancer signaling pathway,MAPK signaling pathway and nuclear factor-κB signal transduction pathway,osteoclast differentiation,TNF signal pathway,etc.Molecular docking showed that the key components of Bushen Huoxue Decoction could spontaneously bind to the key targets of multiple myeloma,and the binding performance of methyl cimicifugin with MAPK14 was the best.Conclusion Bushen Huoxue Decoction can inhibit the proliferation of multiple myeloma cells,enhance the effect of chemotherapy and reduce bone damage through multi-component,multi-target and multi-channel.It has a certain value in the treatment of multiple myeloma.