摘要
目的探索补中益气丸治疗慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)的分子机制。方法在TCMSP中获取补中益气丸活性成分及靶点;以GEO数据库为主,OMIM数据库为辅获取疾病靶点,使用R软件映射出药物-疾病共同靶点。通过Cytoscape 3.7.2绘制药物-成分-共同靶点-疾病网络图,以及基于共同靶点的PPI网络拓扑分析图。使用R软件对共同靶点进行GO功能富集分析、KEGG通路富集分析,并利用KEGG通路富集分析结果构建通路-靶点网络图。最后对活性成分及靶点进行分子对接验证。结果共获得163个补中益气丸活性成分及225个可用于后续分析的靶点,1313个COPD靶点,映射得出药物-疾病共同靶点20个。分析得出补中益气丸治疗COPD主要有槲皮素、山柰酚、豆甾醇等活性成分;涉及δ-阿片受体1(OPRD1)、白细胞介素6(IL-6)、白细胞介素10(IL-10)、表皮生长因子受体(EGFR)、窖蛋白1(CAV1)、热休克蛋白B1(HSPB1)、半胱氨酸天冬氨酸蛋白酶8(CASP8)等作用靶点。GO分析提示主要与氧化应激反应相关;KEGG分析提示主要与肿瘤坏死因子、Toll样受体、低氧诱导因子-1、叉头盒O、Janus激酶-转录激活因子等信号通路有关。最后,分子对接结果证实了活性成分与靶点具有较好的结合能力。结论补中益气丸治疗COPD的分子机制可能是以抗炎与抗氧化应激为核心,兼顾调节免疫、低氧耐受、气道黏液高分泌与保护血管内皮细胞多方面。
Objective To explore the molecular mechanism of Buzhong Yiqi pills in the treatment of chronic obstructive pulmonary disease(COPD).Methods The active ingredients and targets of Buzhong Yiqi pills were screened from TCMSP.The targets of COPD were predicted by the combination of GEO and OMIM databases.And R software was used to map out common drug-disease targets.Cytoscape 3.7.2 was utilized to draw a drug-ingredientcommon target-disease network diagram and the PPI network topology analysis diagram based on the common targets.GO function enrichment analysis and KEGG pathway enrichment analysis on common targets were performed by R software.And pathway-target network diagram was constructed based on the results of KEGG pathway enrichment analysis.Finally,the molecular docking verification of the active ingredients and the targets was carried out.Results A total of 163 active ingredients and 225 targets of Buzhong Yiqi pills,1313 COPD targets were obtained.20 common drug-disease targets were mapped out.The analysis showed that the active ingredients in Buzhong Yiqi pills for the treatment of COPD were quercetin,kaempferol,stigmasterol,etc.It was also involved OPRD1,IL-6,IL-10,EGFR,CAV1,HSPB1,CASP8 and so on.GO analysis suggested that it was mainly related to oxidative stress.By KEGG enrichment analysis,TNF signaling pathway,Toll-like receptor signaling pathway,HIF-1 signaling pathway,FoxO signaling pathway and JAK-STAT signaling pathway were found.Finally,the molecular docking results confirmed that the active ingredients had good binding ability with the targets.Conclusion The molecular mechanism of Buzhong Yiqi pills in the treatment of COPD may be based on anti-inflammatory and antioxidative stress,and taken into account the regulation of immunity,hypoxia tolerance,airway mucus hypersecretion and the protection of vascular endothelial cells.
作者
谢铱子
纪树亮
庄轰发
吴鹏
詹少锋
黄佳佳
黄慧婷
杨柳柳
刘小虹
XIE Yizi;JI Shuliang;ZHUANG Hongfa;WU Peng;ZHAN Shaofeng;HUANG Jiajia;HUANG Huiting;YANG Liuliu;LIU Xiaohong(The First Clinical College,Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;The First Affiliated Hospital,Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2021年第2期182-190,共9页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家自然科学基金项目(81904132)
广东省中医药管理局面上项目(20201092)
广东省教育厅科研项目(2017KQNCX042)
刘小虹广东省名中医传承工作室建设项目(粤中医办函[2018]5号)
广东省省级科技计划项目(华南中医药协同创新中心)(2014B090902002)
B3-9国家临床医学研究中心建设项目(呼吸科)(2110200309)
广州中医药大学学科提升计划:中医内科学肺病方向。
关键词
补中益气丸
慢性阻塞性肺疾病
网络药理学
转录组学
分子对接
Buzhong Yiqipills
chronic obstructive pulmonary disease
network pharmacology
transcriptomics
molecular docking
