基于网络药理学和分子对接探讨补元汤治疗慢性阻塞性肺疾病的作用机理

Mechanism of the Buyuan decoction in the treatment of chronic obstructive pulmonary disease based on network pharmacology and molecular docking

目的:应用网络药理学和分子对接技术探讨补元汤治疗慢性阻塞性肺疾病(Chronic Obstructive Pulmonary Disease,COPD)的作用靶点及分子机制。方法:采用中药系统药理学数据库与分析平台(TCMSP)和HERB数据库收集补元汤的化学成分及可能的相关靶点,从GeneCards、TTD、DrugBank及DisGeNET数据库中获得COPD相关靶点,两者取交集获得补元汤治疗COPD的共同靶点;利用Cytoscape 3.8.2建立药物-化学成分-共同靶点-疾病网络图;STRING 11.5数据库构建蛋白质-蛋白质相互作用网络及提取关键靶点;Metascape数据库通过对关键靶点基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路分析,建立补元汤治疗COPD靶点-信号通路网络;最后通过AutoDockTools 1.5.6软件实现对化学成分和关键靶点分子对接。结果:从补元汤中共获得116个化学成分,预测靶点2108个,其中与COPD有关靶点为872个,两者共同靶点有122个。槲皮素、豆甾醇、山柰酚等是补元汤主要化学成分,白细胞介素(Interleukin,IL)-6、丝氨酸/苏氨酸蛋白激酶(Akt Serine/Threonine Kinase 1,AKT1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等是其关键靶点,并通过晚期糖基化终末产物与其受体(Advanced Glycation End-product-Receptor for Advanced Glycation End Products,AGE-RAGE)、癌症、IL-17、缺氧诱导因子(Hypoxia Inducible Factor,HIF)-1、TNF等多种信号途径对COPD进行治疗。对接结果表明槲皮素和山柰酚与IL-6和AKT1具有明显的结合作用。结论:研究结果显示,国医大师洪广祥经验方补元汤在治疗COPD过程中,具有多成分、多靶点、多途径的特征,同时还可进一步增强COPD患者免疫功能,提高机体的免疫力,为治疗COPD机制提供新的参考和理论基础。

Objective:To explore the target and molecular mechanism of the Buyuan decoction(补元汤)in the treatment of chronic obstructive pulmonary disease(COPD)by network pharmacology and molecular docking technology.Methods:The chemical constituents and possible related targets of the Buyuan decoction were collected using TCMSP and HERB databases,and COPD-related targets were obtained from GeneCards,TTD,DrugBank and DisGeNET databases,and the common target of Buyuan Decoction in the treatment of COPD was obtained by taking the intersection of the two.Use Cytoscape 3.8.2 to build drug-chemical components-common target-disease network map.STRING 11.5 database to build protein interaction(PPI)network and key targets.Metascape database through the GO function enrichment of key targets through analysis and KEGG pathway analysis,the target-signaling pathway network of the Buyuan decoction in COPD treatment was established,finally,the chemical components and key target molecules were docked by AutoDockTools 1.5.6 software.Results:There were 116 chemical constituents were screened from the Buyuan decoction,and 2108 were predicted targets,including 872 COPD-related targets and 122 targets in total.Quercetin,stigmasterol,kaempferol,etc.are the main chemical components of the Buyuan decoction,IL-6,AKT1,TNF,etc.are key targets,and use AGE-RAGE,cancer,IL-17,HIF-1,TNF and other signals approach to the treatment of COPD.The docking results showed that quercetin and kaempferol had obvious binding effects with IL-6 and AKT1.Conclusion:The results of the study show that Professor HONG Guangxiang,a master of TCM experience prescription the Buyuan decoction has the characteristics of multi-component,multi-target and multi-channel in the treatment of COPD.At the same time,it can further enhance the immune function of patients with COPD and improve the immune.It provides a new reference and theoretical basis for the treatment of COPD mechanism.