基于网络药理学和分子对接探讨参苓白术散治疗COPD骨骼肌功能障碍的作用机制

Based on Network Pharmacology and Molecular Docking to Explore the Mechanism of Shenlingbaizhu Powder in the Treatment of COPD Muscular Dystrophy

目的:本研究旨在利用网络药理学与分子对接技术,深入探索参苓白术散在COPD肌营养不良(骨骼肌功能障碍)治疗中的作用机制及其相关活性成分,从而为临床应用提供更多可能性。研究方法:首先,利用TCMSP检索参苓白术散的组成成分,包括白芍、白扁豆、桔梗、人参、茯苓、甘草、莲子心、山药、薏苡仁、砂仁等十种中药,并确定其所含的有效成分以及其作用靶点。然后,利用String数据库和Cytoscape3.6.1软件,构建参苓白术散治疗COPD肌功能障碍的蛋白互作(PPI)网络,并研究其中Hub网络的特征,最后,利用KEGG富集技术,对参苓白术散的药理活性进行深入探究,以期发现其在COPD患者康复过程中的潜在机制。通过使用Chem Office、Vina和AutoDock等工具,我们可以有效地进行分子整合。结果:设定筛选标准为口服生物利用率(OB)>30%、类药性(DL)>0.18共获得130个活性成份,共检测到黄参苓白术散治疗COPD肌营养不良的潜在靶点共232个,其中关键靶点共22个,并通过对KEGG通道的分析获得了122条通道,筛选得到治疗COPD肌营养不良的25条主要通路。结论:参苓白术散中的活性化合物能通过抑制FOXO1、碳酸酐酶Ⅲ抗体、血管紧张素转化酶的表达,提高AMP激活的蛋白激酶的表达,作用于MAPK8、MAPK14等靶点,调节多条信号通路,起到治疗COPD肌营养不良(骨骼肌功能障碍)的作用。

Objective:To explore the effective pathway and active compounds of Shenlingbaizhu Powder on COPD muscular dystrophy(skeletal muscle dysfunction),using network pharmacology and molecular docking technology,with a purpose to enlighten its clinical application.Methods:All the active components and action targets of Radix Paeoniae Alba,White lentil,Platycodon grandiflorum,Ginseng,Poria,Glycyrrhiza uralensis Lotus seed,Yam,Coix seed and Amomum villosum were searched from the traditional Chinese Medicine system Pharmacological Data Analysis platform(TCMSP).String database and Cytoscape3.6.1software were used to construct the protein interaction network of Shenlingbaizhu Powder in the treatment of COPD muscle dysfunction,obtain the Hub network in PPI network,and analyze the KEGG enrichment pathway.And use ChemOffice,PyMOL,AutoDock software for molecular Docking.Results:A total of 130 active components were obtained according to the screening criteria of oral bioavailability(OB)>30%and DL>0.18.A total of 232 potential targets of Huangshen Ling Baizhu Powder in the treatment of COPDmuscular dystrophy were detected,of which 22 were key targets.122 channels were obtained through the analysis of KEGG channels,and 25 main pathways for the treatment of COPD muscular dystrophy were screened.Conclusion:The active compounds in Shenling Baizhu Powder can inhibit the expression of FOXO1,carbonic anhydraseⅢantibody and angiotensin converting enzyme,increase the expression of AMP activated protein kinase,act on MAPK8,MAPK14 and other targets,regulate multiple signal pathways,and play a role in the treatment of COPD muscular dystrophy(skeletal muscle dysfunction).