摘要
利用网络药理学和生物信息学技术预测附子理中丸治疗溃疡性结肠炎(ulcerative colitis,UC)的作用机制。选取附子理中丸中26个入血成分(23个原型化合物及3个代谢产物)为研究对象,利用PharmMapper数据库、SwissTargetPrediction平台、GeneCards和OMIM数据库筛选及预测附子理中丸入血成分的潜在作用靶点;运用String数据库和Cytoscape软件构建蛋白相互作用(PPI)网络模型;运用DAVID平台、KEGG及Reactome数据库对潜在靶点进行GO分析和通路分析;应用Cytoscape软件构建"药物成分-作用靶点-作用通路"网络;使用AutoDock vina软件对入血成分与关键靶点进行分子对接。结果得到附子理中丸治疗UC的潜在靶点82个,靶点主要涉及有机物反应、细胞凋亡的调节、细胞程序性死亡的调控等生物过程,通过参与癌症、结直肠癌、血管内皮生长因子(vascular endothelial growth factor,VEGF)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)和花生四烯酸代谢等信号通路来发挥治疗UC的作用。本研究从网络药理学的角度预测了附子理中丸治疗UC的作用机制,表明附子理中丸治疗UC具有多成分、多靶点和多途径的特点,为进一步深入研究其作用机制奠定了基础。
Network pharmacology and bioinformatics technology were used to predict the mechanism of action of Fuzi-Lizhong pill(FLP)in the treatment of ulcerative colitis(UC).26 components(23 prototype compounds and 3 metabolites)in the blood of FLP were selected as the research objects.PharmMapper database,SwissTargetPrediction platform,GeneCards and OMIM database were used to screen and predict potential targets of FLP in blood.The protein-protein interaction network model was constructed by using String database and Cytoscape software.DAVID platform,KEGG and Reactome databases were used for GO analysis and pathway analysis of potential targets.Network of drug ingredients-targets-pathways was constructed by Cytoscape software.AutoDock vina software was used to dock the molecules of the absorbed ingredients of FLP in blood with the key targets.82 potential targets of FLP for treatment of UC were obtained.Potential targets mainly involve biological processes such as response to organic substance,regulation of apoptosis,regulation of programmed cell death,which played roles in the treatment of UC by adjusting pathways in cancer,Colorectal cancer,Vascular endothelial growth factor signaling pathway,Mitogen-activated protein kinase signaling pathway,arachidonic acid metabolism and the other signal pathways.From the perspective of network pharmacology,this study predicted the mechanisms of action of FLP in treating UC,indicating that FLP in treating UC had the characteristics of multiple ingredients,multiple targets and multiple pathways,which laid a foundation for further research.
作者
黄友
杨莎莎
林夏
赵生嘉
魏馨怡
傅超美
张臻
HUANG You;YANG Sha-sha;LIN Xia;ZHAO Sheng-jia;WEI Xin-yi;FU Chao-mei;ZHANG Zhen(State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China,School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China)
出处
《药学学报》
CAS
CSCD
北大核心
2020年第8期1812-1822,共11页
Acta Pharmaceutica Sinica
基金
国家自然科学基金青年科学基金项目(81803742)
四川省教育厅自然科学重点项目(18ZA0187)
成都中医药大学自然基金预研项目(ZRYY1718)
成都中医药大学杏林学者青年学者专项(QNXZ2019031)。
关键词
网络药理学
分子对接
附子理中丸
溃疡性结肠炎
潜在靶点
作用通路
network pharmacology
molecular docking simulation
Fuzi-Lizhong pill
ulcerative colitis
potential target
pathway
