大柴胡汤治疗结石性胆囊炎的网络药理学研究及分子对接验证

Network Pharmacology Study and Molecular Docking Verification of Dachaihu Decoction in the Treatment of Calculous Cholecystitis

目的:基于网络药理学和分子对接的方法探讨大柴胡汤治疗胆囊炎(Cholecystitis)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)检索相关文献获得大柴胡汤所含中药的主要化学成分,收集其相对应的靶点;胆囊炎疾病靶点来源于GeneCards、在线人类孟德尔遗传(OMIM)、PharmGkb数据库。结合Cytoscape 3.8.0构建药物-核心靶点-有效成分网络、靶标蛋白质-蛋白质相互作用(PPI)网络。利用Bioconductor中的R包对核心靶标进行基因本体(GO)富集和京都基因与基因组百科全书(KEGG)通路分析。结果:获得大柴胡汤活性成分151个,药物靶点260个;疾病靶点485个;交集基因55个;PPI网络分析发现,核心蛋白涉及TNF-α、CCK、EGFR、AKT1、VEGFA;GO富集分析得到2307个GO条目。大柴胡汤包含细胞组分92个,生物过程2126个,分子功能89个,主要有受体配体活性、细胞因子活性、细胞因子受体结合、磷酸酶结合等;KEGG通路富集分析发现大柴胡汤主要涉及AGE-RAGE信号通路、白细胞介素-17信号通路以及HIF-1信号通路等。结论:通过网络药理学分析发现,大柴胡汤多成分、多靶点调控机体,通过多途径起到治疗结石性胆囊炎的作用。

Objective:To explore the mechanism of Dachaihu Decoction in the treatment of cholecystitis based on network pharmacology and molecular docking.Methods:the main chemical constituents of Dachaihu Decoction were obtained from TCMSP and related literature,and the corresponding targets were collected;the targets of cholecystitis were from GeneCards,OMIM and PharmGKB databases.Combined with Cytoscape 3.8.0,the drug core target active component network was constructed,and the target protein interacted with PPI network.The r-packet of Bioconductor was used to enrich go and analyze KEGG pathway.Results:A total of 151 active components and 260 drug targets of Dachaihu Decoction were obtained;485 disease targets were obtained;55 intersection genes were obtained;PPI protein network analysis showed that core proteins involved TNF-α,CCK,EGFR,AKT1,VEGFA;and 2307 go entries were enriched in go.There were 92 cell components,2126 biological processes and 89 molecular functions,mainly including receptor ligand activity,cytokine activity,cytokine receptor binding,phosphatase binding,etc.;KEGG pathway enrichment analysis found that it mainly involved age-rage signaling pathway,interleukin-17 signaling pathway and HIF-1 signaling pathway.Conclusion:through the analysis of network pharmacology,Dachaihu Decoction has the effect of treating calculous cholecystitis by multi-component and multi-target regulation.