基于网络药理学知母-黄柏药对治疗糖尿病作用机制  

Mechanism of Drug Pair Containing Rhizoma Anemarrhenae and Cortex Phellodendri on Treatment of Diabetes Mellitus Based on Network Pharmacology

作　　者：赵灿 杨金伟 吴勇军 喻嵘 ZHAO Can;YANG Jinwei;WU Yongjun;YU Rong(Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine,Hu′nan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大中医方证研究转化医学湖南省重点实验室,长沙410208

出　　处：《世界中医药》2020年第22期3369-3374,3382,共7页World Chinese Medicine

基　　金：国家自然科学基金项目(81573956);国家重点研发计划中医药现代化研究重点专项(2018YFC1704300,2018YFC1704400)。

摘　　要：目的:探讨知母-黄柏药对治疗糖尿病(DM)的作用机制。方法:通过TCMSP、化学专业数据库检索知母、黄柏化学成分和作用靶点,并在UniProt数据库中进行靶点与基因转换,通过OMIM、Drugbank数据库查询现有DM相关基因。进而运用Cytoscape 3.7.1构建成分-靶点网络、靶点相互作用(PPI)网络并进行网络拓扑分析,最后通过Omicshare进行基因GO功能富集分析和KEGG通路富集分析,研究其作用机制。结果:成分-靶点网络共有127个化合物和107个靶点,其中关键化合物涉及槲皮素、豆甾醇、山柰酚等。PPI网络包含107个蛋白,其中关键靶蛋白涉及INS、AKT1、IL6、VEGFA、TNF等。GO功能富集分析得到2612个条目(P<0.05),其中生物过程(BP)条目2125个,分子功能(CC)条目138个,细胞组成(MF)条目349个。KEGG通路富集分析筛选到157个信号通路(P<0.05),涉及到MAPK信号通路、流体剪切应力与动脉粥样硬化、AGE-RAGE信号通路、胰岛素抵抗等信号通路。结论:知母-黄柏中的主要治疗糖尿病活性成分是槲皮素、豆甾醇、山柰酚,靶点主要涉及INS、AKT1、IL6、VEGFA、TNF等,通过MAPK信号通路、AGE-RAGE信号通路、胰岛素抵抗等信号通路协同治疗DM。Objective:To investigate the mechanism of diabetes mellitus(DM)treatment by drug pair containing Rhizoma Anemarrhenae and Cortex Phellodendri.Methods:The chemical constituents and targets of Rhizoma Anemarrhenae and Cortex Phellodendri was searched through TCMSP and chemical professional databases,and target and gene conversion were performed in the UniProt database,and existing DM related genes were checked through OMIM and Drugbank databases.Then Cytoscape 3.7.1 was used to construct a component-target network,a target interaction(PPI)network and perform network topology analysis.Finally,Omicshare was used to perform gene GO function enrichment analysis and KEGG pathway enrichment analysis to study its mechanism of action.Results:The compound-target network contained 127 compounds and 107 targets,and key compounds involved quercetin,stigmasterol,kaempferol,etc.The PPI network contained 107 proteins,and key target proteins involved in INS,AKT1,IL6,VEGFA,TNF,etc.The functional enrichment analysis of GO obtained 2612 items(P<0.05),of which there were 2125 biological process(BP)items,138 molecular function(CC)items,and 349 cell composition(MF)items.There were 157 signaling pathways(P<0.05),involving MAPK signaling pathway,fluid shear stress and atherosclerosis,AGE-RAGE signaling pathway,and insulin resistance and other signal pathways.Conclusion:The main therapeutic active compound of diabetes in Rhizoma Anemarrhenae and Cortex Phellodendri are quercetin,stigmasterol and kaempferol.The targets mainly involve INS,AKT1,IL6,VEGFA,TNF,etc.Through the MAPK signaling pathway,AGE-RAGE signaling pathway,insulin resistance and other signaling pathways,DM is co treated.s.

关 键 词：知母 黄柏 糖尿病 网络药理学 靶点 基因 信号通路 

分 类 号：R285[医药卫生—中药学] R255.4[医药卫生—中医学]