基于网络药理学和分子对接方法探讨雷公藤对狼疮性肾炎的效毒作用机制

Study on the mechanism of toxic effect of Tripterygium wilfordii on lupus nephritis based on network pharmacology and molecular docking

目的基于网络药理学和分子对接方法探讨雷公藤治疗狼疮性肾炎的效毒作用机制。方法通过TCMSP、Uniprot、STITCH等数据库查询雷公藤的化合物分子及其主要靶点,并与狼疮性肾炎相关基因做对比,获得药物靶点与疾病相关的共有基因,构建药物与疾病之间的网络关系。通过String数据库获取潜在作用靶标之间的相互作用关系,利用Cytoscape软件构建中药-成分-疾病网络。运用Clusterprofiler程序分别进行GO基因富集分析和KEGG通路富集分析。结果从雷公藤中筛选得到44个候选活性成分,包括雷公藤甲素、雷公藤多苷、雷公藤红素等;潜在作用靶标228个,其中治疗靶标152个,毒性靶标76个。GO富集分析结果显示,治疗靶标主要与细菌来源分子的反应(response to molecule of bacterial origin)、对脂多糖的反应(response to lipopolysaccharide)、胞浆钙离子浓度的正调控(positive regulation of cytosolic calcium ion concentration)等有关。治疗狼疮性肾炎的相关基因参与通路共125条,具有潜在不良反应的相关基因通路共130条。分子对接结果表明,5α-benzoyl-4α-hydroxy-1β,8α-dinicotinoyl-dihydro-agarofuran、triptofordin B1、triptofordinine A2与SYK有较好的结合性。结论基于网络药理学方法和分子对接挖掘雷公藤对狼疮性肾炎治疗靶点和毒性靶点、治疗作用通路和毒性作用通路,为研究雷公藤对狼疮性肾炎效毒作用机制提供了新的研究方法。

Objective To explore the possible mechanism of Tripterygium wilfordii in treatment of lupus nephritis based on network pharmacology and molecular docking methods. Methods The main active components and the targets of Tripterygium wilfordii were searched and screened from TCMSP, Uniprot, and STITCH databases. By comparing with lupus nephritis related genes, common genes related to drug targets and diseases were obtained, and the network relationship between drugs and diseases was constructed. The interaction relationship between potential targets was obtained by String database, and the network of TCM-component-disease was constructed by Cytoscape software. Clusterprofiler program was used to analyze GO gene enrichment and KEGG pathway enrichment respectively. Results Forty-four candidate active ingredients were screened from Tripterygium wilfordii, mainly including triptolide,tripterygium glycosides, and celastrol. There were 228 potential targets, including 152 therapeutic targets and 76 bacterial origin,response to lipopolysaccharide, positive regulation of cytosolic calcium ion concentration. There were 125 related gene pathways involved in the treatment of lupus nephritis, and 130 related gene pathways with potential adverse reactions. Molecular docking results show that, 5 alpha-benzoyl-4 alpha-hydroxy-1 beta, 8 Alpha-dinicotinoyl-Dihydro-Agarofuran, Triptofordin B1, Triptofordinine A2 showed good binding properties to SYK. Conclusion Based on the methods of network pharmacology and molecular docking, the therapeutic target, toxic target, therapeutic pathway and toxic pathway of Tripterygium wilfordii on lupus nephritis provide a new research method for the study of the mechanism of Tripterygium wilfordii.