基于网络药理学探讨隔山消积颗粒治疗功能性消化不良的物质基础及作用机制

Material Basis and Mechanism of Geshan Xiaoji Granules in the Treatment of Functional Dyspepsia Based on Network Pharmacology

目的探讨苗药复方隔山消积颗粒治疗功能性消化不良(FD)的物质基础及作用机制。方法通过文献检索隔山消积颗粒的化学成分,采用ADMETlab 2.0软件筛选活性成分;运用SwissTargetPrediction数据库预测其作用靶标,并与GenCLip3数据库和GeneCards数据库获得的FD相关靶标叠合,获取治疗FD的靶标。构建药味-活性成分-靶标相互作用网络,筛选关键活性成分和靶标。采用String数据库获得靶标-靶标相互作用网络,运用David数据库对靶标进行GO聚类分析和KEGG通路富集分析。采用分子对接技术考察活性成分与靶标间的结合亲和力和作用模式。结果筛选105个苗药复方隔山消积颗粒活性成分,作用于293个FD相关靶标。药味-活性成分-靶标相互作用网络分析筛选出度值大于中介值(12.3645)的关键活性成分70个和关键靶标61个。GO聚类分析显示,关键作用靶标主要参与信号转导、凋亡过程的负调控、蛋白质结合、ATP结合等生物过程;KEGG通路富集分析结果显示,上述靶标主要通过调控逆行内源性大麻素信号、胆碱能突触、花生四烯酸代谢和TRP通道的炎性介质调节等通路。分子对接结果表明,隔山消积颗粒活性成分与FD关键靶标有较强亲和力。结论苗药复方隔山消积颗粒的潜在活性成分为告达亭、芫花素、开德苷元、罗索他明、汉黄芩素和加加米宁等,通过调控胃肠动力障碍、脑-肠轴功能紊乱和精神心理因素等相关通路治疗FD。

Objective To investigate the material basis and mechanism of Miao medicine compound Geshan Xiaoji Granules in the treatment of functional dyspepsia(FD).Methods The chemical ingredients of Geshan Xiaoji Granules were searched by studies,and the active ingredients were screened by the ADMETlab 2.0 software.The action targets of active ingredients were predicted by the SwissTargetPrediction database,and the FD-related targets obtained from the GenCLip 3 and GeneCards databases were overlapped with the above the action targets of active ingredients to obtain the targets in the treatment of FD.The drugs-active ingredients-targets interaction network was constructed to screen the key active ingredients and targets.The targets-targets interaction network was obtained by the String database,and the gene ontology(GO)clustering analysis and the Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of the targets were conducted by the David database.The binding affinity and action mode between the active ingredients and the targets were investigated by the molecular docking technology.Results A total of 105 active ingredients of Miao medicine compound Geshan Xiaoji Granules were screened,which acted on 293 FD-related targets.A total of 70 key active ingredients and 61 key targets with a degree greater than the betweenness(12.3645)were screened by the drugs-active ingredients-targets interaction network.The results of GO clustering analysis showed that the key targets were mainly involved in the biological processes such as signal transduction,negative regulation of apoptosis process,protein binding and ATP binding.The results of KEGG pathway enrichment analysis showed that the above targets mainly regulated the pathways such as retrograde endocannabinoid signaling,cholinergic synapse,arachidonic acid metabolism and inflammatory mediator regulation of TRP channels.The results of molecular docking showed that the active ingredients of Geshan Xiaoji Granules had strong affinity with the key targets of FD.Conclusion The potential active ingredients of Miao medicine compound Geshan Xiaoji Granules are caudatin,genkwanin,kidjolanin,rostratamine,wogonin and gagamine,which can treat FD by regulating related pathways such as astrointestinal motility disorder,brain-gut axis dysfunction and psychosocial factors.