基于网络药理学和分子对接分析大黄治疗急性胰腺炎的分子作用机制

Molecular mechanism of rhubarb in treatment of acute pancreatitis based on network pharmacology and molecular docking

目的运用网络药理学和分子对接分析大黄治疗急性胰腺炎(acute pancreatitis,AP)的分子作用机制。方法运用TCMSP、TCMID、Swiss Target Prediction数据库筛选大黄的活性成分及靶点,GeneCards、OMIM数据库筛选AP的靶点。然后利用Cytoscape软件构建大黄“活性成分-药物靶点”网络、大黄治疗AP的“活性成分-疾病靶点”网络,在STRING数据库构建PPI网络,Metascape数据库和R语言进行GO和KEGG富集分析。最后通过分子对接验证前期所得的核心活性成分与核心靶点结合的可能性。结果查询得到大黄活性成分192个,AP靶点1882个。大黄治疗AP主要且核心的前3个活性成分为beta-sitosterol、aloe-emodin、EUPATIN,大黄治疗AP核心靶点为HSP90AA1。GO富集分析集中于对有毒物质反应等,KEGG富集分析则显著富集在与AP密切相关的p53信号通路。分子对接显示结合性好、构象稳定。结论大黄可通过p53信号通路影响与AP相关的基因、蛋白表达,从而抑制细胞凋亡,缓解AP的炎症损伤。

Aim To analyze the molecular mechanism of rhubarb in the treatment of acute pancreatitis(AP)by network pharmacology and molecular docking.Methods TCMSP,TCMID and Swiss target prediction databases were used to screen the active components and targets of rhubarb,and genecards and OMIM databases were used to screen the targets of AP.Then the active ingredient drug target network of rhubarb and theactive ingredient disease target network of rhubarb for AP were constructed by using Cytoscape software.PPI network was constructed in string database,and go and KEGG enrichment analysis was performed in metascape database and R language.Finally,molecular docking was used to verify the possibility of binding the core active components to the core target.Results A total of 192 active components and 1882 AP targets were obtained.The first three active components of rhubarb in the treatment of AP were beta sitosterol,aloe emodin and eupatin.The core target of rhubarb in the treatment of AP was hsp90aa1.Go enrichment analysis focused on reaction to toxic substances,while KEGG enrichment analysis was significantly enriched in p53 signaling pathway closely related to AP.Molecular docking showed good binding and stable conformation.Conclusions Rhubarb can affect the expression of AP related genes and proteins through p53 signaling pathway,thereby inhibiting cell apoptosis and alleviating the inflammatory injury of AP.