基于分子对接与数据挖掘探讨生姜解半夏毒的相关机制

Mechanism of Zingiberis Rhizoma Recens in Detoxification of Pinelliae Rhizoma Based on Molecular Docking and Data Mining

目的:基于分子对接与数据挖掘研究生姜解半夏毒的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)检索生姜有效成分,通过SwissTargetPrediction数据库预测生姜成分靶点,经Swiss-model同源建模半夏凝集素后进行分子对接。通过DisGeNET数据库获取炎症相关靶点,通过基因映射获取生姜治疗炎症的作用靶点。应用String构建靶点蛋白质-蛋白质相互作用(PPI)网络并筛选关键基因。对靶点基因进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析。结果:筛选得到生姜有效成分5种,与半夏凝集素均有较强结合力。生姜治疗炎症靶点49个,关键靶点有15个,包括MMP9、HSP90AA1、PPARG、RELA、APP、ICAM1、MMP2、mTOR等。通过GO与KEGG富集分析,49个靶点基因涉及急性炎症反应、炎症反应的调节、炎症介质的产生、T细胞的激活、淋巴细胞迁移生物过程,且主要富集于Th17细胞分化相关通路。结论:生姜对半夏毒性成分产生抑制作用并通过减轻炎症反应来发挥解毒作用。

Objective:To explore the mechanism of Zingiberis Rhizoma Recens in the detoxification of Pinelliae Rhizoma based on molecular docking and data mining.Methods:The chemical ingredients of Zingiberis Rhizoma Recens were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The targets related to Zingiberis Rhizoma Recens were predicted from SwissTargetPrediction.Molecular docking was carried out after homologous modeling of agglutinin from Pinelliae Rhizoma by Swiss-model.Targets related to inflammation were screened out from DisGeNET,and the targets of Zingiberis Rhizoma Recens against inflammation were obtained by gene mapping.The protein-protein interaction(PPI)network of Zingiberis Rhizoma Recens in the treatment of inflammation was delineated by String,and the key genes were screened out.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on target genes.Results:Five types of active compounds of Zingiberis Rhizoma Recens had strong binding force with agglutinin from Pinelliae Rhizoma.There were 49 targets of Zingiberis Rhizoma Recens in the treatment of inflammation,and 15 were key ones,including MMP9,HSP90AA1,PPARG,RELA,APP,ICAM1,MMP2,and mTOR.As revealed by GO and KEGG enrichment analyses,49 target genes were involved in biological processes such as acute inflammatory response,regulation of inflammatory response,inflammatory mediator production,T cell activation,and lymphocyte migration,and mainly enriched in the signaling pathways related to Th17 cell differentiation.Conclusion:Zingiberis Rhizoma Recens can inhibit the toxicity produced by Pinelliae Rhizoma by reducing inflammatory responses.