药学学报, 2019, 54(11): 1982-1989
引用本文:
袁文彬, 韦艳美, 陈勇, 梁继超. 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[J]. 药学学报, 2019, 54(11): 1982-1989.
YUAN Wen-bin, WEI Yan-mei, CHEN Yong, LIANG Ji-chao. Mechanisms of eleutheroside for treatment of diabetes mellitus type 2 based on network pharmacology[J]. Acta Pharmaceutica Sinica, 2019, 54(11): 1982-1989.

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
袁文彬, 韦艳美, 陈勇, 梁继超
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, 湖北 武汉 430062
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(polyclonalantibody 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。
关键词:    网络药理学      刺五加总苷      2型糖尿病      作用机制      靶点     
Mechanisms of eleutheroside for treatment of diabetes mellitus type 2 based on network pharmacology
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
Abstract:
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 these 7 components that are related to diabetes mellitus type 2. Then we used cytoscape 3.6.1 to build a "component-target" 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 "component-target-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.
Key words:    network pharmacology    eleutheroside    diabetes mellitus type 2    mechanism    target   
收稿日期: 2019-05-05
DOI: 10.16438/j.0513-4870.2019-0350
基金项目: 国家自然科学基金资助项目(81400791).
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