基于网络药理学及分子对接技术研究人参-陈皮配伍治疗慢性阻塞性肺疾病的作用机制

Based on Network Pharmacology and Molecular Docking Technology to Study the Mechanism of Panax Ginseng and Citrus Reticulata Pericarpium in the Treatment of Chronic Obstructive Pulmonary Disease

目的研究人参-陈皮配伍治疗慢性阻塞性肺疾病(COPD)的主要活性成分和潜在的分子作用机制。方法从TCMSP数据库中获取人参、陈皮的活性成分和潜在靶点,疾病靶点利用DrugBank、TTD、GeneCards数据库获取。“药物-化合物-靶点”互作网络可视化由Cytoscape3.6.1软件完成。通过绘制韦恩图得到人参、陈皮和COPD的共有靶点,运用Cytoscape平台获取共有靶点相互作用关系。通过DAVID数据库对共有靶点进行GO、KEGG富集分析。活性成分和关键靶点的分子对接由autodock vina实现,并采用体外抗炎活性实验进行验证。结果从人参和陈皮中共筛选得到27个活性成分,800个疾病靶点,药物和疾病共有靶点70个。GO功能富集分析得到GO条目213个(P<0.01),KEGG通路富集筛选得到99条信号通路(P<0.01)。分子对接结果显示,甾醇类成分和黄酮类成分与关键靶点有较高的结合性。体外抗炎活性验证结果表明,川陈皮素、山奈酚、柚皮素、人参皂苷rh2能够减少炎症因子的分泌。结论人参-陈皮配伍可通过多成分、多靶点和多通路调控炎症因子释放,达到治疗COPD的效果。

Objective To study the main active components and potential molecular mechanism of Panax Ginseng and Citrus Reticulata Pericarpium in the treatment of COPD.Methods The active ingredients and potential targets of Panax Ginseng and Citrus Reticulata Pericarpium were obtained from the TCMSP database and disease targets,accessed using DrugBank,TTD,and GeneCards databases.The network visualization of"drug-compound-target"interaction was accomplished by Cytoscape 3.6.1 software.The common targets of Panax Ginseng and Citrus Reticulata Pericarpium of COPD were obtained by drawing the Wayne diagram.Cytoscape software was used to obtain the interaction relationship between common targets.GO and KEGG enrichment analysis was performed on the common targets through DAVID database.The molecular docking of the active ingredient and the key target was realized by Autodock Vina and verified by the in vitro anti-inflammatory activity experiment.Results A total of 27 active ingredients,800 disease targets and70 common drug and disease targets were selected from Panax Ginseng and Citrus Reticulata Pericarpium.GO functional enrichment analysis yielded 213 GO items(P<0.01),and KEGG pathway enrichment screening yielded 99 signal pathways(P<0.01).The results of molecular docking showed that sterols and flavonoids had higher binding properties with the key targets.The results of in vitro anti-inflammatory activity validation showed that nobiletin,kaempferol,naringenin and ginsenoside rh2 could reduce the secretion of inflammatory factors.Conclusion Panax Ginseng and Citrus Reticulata Pericarpium compatibility can regulate the release of inflammatory factors through multiple components,multiple targets and multiple pathways to achieve the therapeutic effect of COPD.