基于网络药理学对刺五加总苷治疗2型糖尿病作用机制研究  

Mechanisms of eleutheroside for treatment of diabetes mellitus type 2 based on network pharmacology

作　　者：袁文彬 韦艳美 陈勇[1] 梁继超[1] YUAN Wen-bin;WEI Yan-mei;CHEN Yong;LIANG Ji-chao(Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine,National and Local Joint Engineering Research Center of High-throughput Drug Screening Technology,Hubei University,Wuhan 430062,China)

机构地区：[1]湖北大学中药生物技术湖北省重点实验室药物高通量筛选技术国家地方联合工程研究中心

出　　处：《药学学报》2019年第11期1982-1989,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81400791)

摘　　要：本文以刺五加总苷中的7种主要成分为研究对象,利用网络药理学方法对刺五加总苷治疗2型糖尿病(diabetes mellitus type 2)的作用机制进行探讨。首先运用SwissTargetPrediction、GeneCard、String平台在线预测这7种成分与2型糖尿病相关的潜在靶点共35个。然后使用Cytoscape3.6.1构建"成分-靶点"网络图,并利用内置的Networkanalyzer工具进行拓扑学分析。在DAVID6.8平台上进行基因功能(gene ontology,GO)富集分析和KEGG通路富集分析,根据富集结果构建"成分-靶点-通路"网络图。并筛选出可能主要作用于2型糖尿病的成分作为核心成分,然后将核心成分与关键疾病靶蛋白进行分子对接验证,并深入分析刺五加总苷作用的潜在机制。结果经筛选,共有8条与2型糖尿病相关的重要通路。本研究表明,刺五加苷A、刺五加苷D、刺五加苷E和芝麻素在胰岛素抵抗、细胞凋亡和炎症相关通路起关键作用。刺五加总苷可能主要通过作用信号转导子和转录激活子(signal transducer and activator of transcription,STATs)、非受体型蛋白酪氨酸磷酸酶(polyclonal antibody to protein tyrosine phosphatase,non receptor type,PTPN)1、PTPN2、c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)、p38蛋白等靶点,通过多通路的方式共同作用,起到对2型糖尿病的综合治疗效果,并为今后的刺五加总苷作为抗2型糖尿病药物的开发奠定了基础。Seven main components in eleutheroside were used as research objects,and the mechanism of action of total eleutheroside for treatment of diabetes mellitus type 2 was investigated by network pharmacology.The SwissTargetPrediction,GeneCard,and String platforms were used to predict the 35 potential targets of these7 components that are related to diabetes mellitus type 2.Then we used cytoscape 3.6.1 to build a"componenttarget"network map and used the Networkanalyzer tool for topology analysis.Gene ontology(GO)enrichment analysis and KEGG pathway enrichment analysis were performed on the DAVID6.8 platform,and the"componenttarget-path"network map was constructed based on the enrichment results.Those components mainly used in diabetes mellitus type 2 were screened as core components,and the core components were docked with key disease target proteins to verify the potential mechanism of the total eleutheroside.After screening,8 important pathways associated with diabetes mellitus type 2 were identified.This study showed that eleutheroside A,eleutheroside D,eleutheroside E and sesamin played key roles in insulin resistance,apoptosis and inflammation pathways.The total eleutheroside may ameliorate type 2 diabetes mainly through regulating signal transducer and activator of transcription factors(STATs),non-receptor protein tyrosine phosphatase(PTPN)1,PTPN2,c-Jun N-terminal kinase(JNK),and p38 mitogen activate protein kinase.These components worked together through multiple signaling pathway.Based on our data,eleutheroside is proposed as a novel therapeutic strategy for treatment of type 2 diabetes.

关 键 词：网络药理学 刺五加总苷 2型糖尿病 作用机制 靶点 

分 类 号：R966[医药卫生—药理学]