基于网络药理学及分子对接分析疮灵液治疗慢性难愈性创面的作用机制

Analysis of the mechanism of Chuangling liquid in the treatment of chronic refractory wound based on network pharmacology and molecular docking

目的本研究通过网络药理学及分子对接分析疮灵液治疗慢性难愈性创面(CRW)的作用机制。方法收集疮灵液组成中药活性成分的对应靶点及CRW的疾病靶点,以确定交集靶点,利用STRING在线平台绘制共同靶点的蛋白质相互作用(PPI)网络图及拓扑确定核心靶点,通过Cytoscape软件制作中药—活性成分—靶点网络图。利用DAVID数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,AutoDockTools进行核心靶点与有效成分的分子对接。结果获得疮灵液32个有效活性成分及225个对应靶点,筛选出3997个CRW相关靶点,疮灵液治疗CRW的潜在靶点177个。潜在作用通路为TNF信号通路、内分泌阻力、细胞凋亡、PI3K-AKT信号通路等。分子对接验证TP53、AKT1和对应成分之间具有良好的结合活性。结论疮灵液可能通过作用于TP53、AKT1受体,调控PI3K-AKT-P53通路,从而发挥治疗CRW的作用,为疮灵液治疗CRW提供了理论指导。

Objective To analyze the mechanism of Chuangling liquid in the treatment of chronic refractory wound(CRW)through network pharmacology and molecular docking.Methods The corresponding targets of the active ingredients of traditional Chinese medicine and the disease targets of CRW were collected to determine the intersection targets.The protein-protein interaction(PPI)network map of common targets and the topology were drawn by STRING online platform to determine the core targets.The traditional Chinese medicine active ingredient target network map was made by Cytoscape software.DAVID database was used for GO and KEGG enrichment analysis,and AutoDockTools was used for molecular docking of core targets and active ingredients.Results A total of 32 active ingredients and 225 corresponding targets of Chuangling liquid were obtained,3997 CRW related targets were screened,and 177 potential targets of Chuangling liquid in the treatment of CRW were identified.The potential pathways were TNF signaling pathway,endocrine resistance,apoptosis,PI3K-AKT signaling pathway,etc.Molecular docking verified that TP53,AKT1 and the corresponding components had good binding activity.Conclusion Chuangling liquid may regulate PI3K-AKT-P53 pathway by acting on TP53 and AKT1 receptors,thus playing a role in the treatment of CRW,which provides theoretical guidance for Chuangling liquid in the treatment of CRW.