基于网络药理学和分子对接探讨枇杷叶防治Ⅱ型糖尿病的作用机制  

Mechanism of Loquat Leaf on Type 2 Diabetes Based on Network Pharmacology and Molecular Docking

作　　者：孔红铭 叶嘉昕 赵雅婷 赵楠星 夏旭东 戚向阳[1] 陈秋平[1] KONG Hongming;YE Jiaxin;ZHAO Yating;ZHAO Nanxing;XIA Xudong;QI Xiangyang;CHEN Qiuping(College of Biological and Environmental Sciences,Zhejiang Wanli University,Ningbo,Zhejiang 315100)

机构地区：[1]浙江万里学院生物与环境学院,浙江宁波315100

出　　处：《核农学报》2022年第12期2436-2446,共11页Journal of Nuclear Agricultural Sciences

基　　金：浙江省一流学科“生物工程”学生创新项目(CX2021033);国家级大学生创新训练项目(202110876052)。

摘　　要：为探究枇杷(Eriobotrya japonica)叶用于防治Ⅱ型糖尿病的作用机理,本研究采用网络药理学与分子对接技术,利用TCMSP、Uniprot、Genecards、Venny 2.1.0、DAVID等数据库检索枇杷叶与Ⅱ型糖尿病的共同靶点,绘制相互作用关系网络图,并进行基因本体论(GO)及京都基因与基因组百科全书(KEGG)富集分析;通过AutoDock Tools进行分子对接验证。从TCMSP数据库收集得到19种活性成分和294个相关靶点,通过Venny 2.1.0数据库得到89个Ⅱ型糖尿病与枇杷叶活性成分的交集靶点,对应表没食子儿茶素没食子酸酯(EGCG)、槲皮素、山奈酚、β-谷甾醇等10个活性物质,进而构建了“活性成分-疾病靶点”网络图。研究发现,枇杷叶活性成分主要通过调节氧化应激反应、丝氨酸/苏氨酸激酶活性、对脂多糖反应和上皮细胞增殖等来调控晚期糖基化产物-晚期糖基化终产物受体(AGE-RAGE)、缺氧诱导因子-1(HIF-1)和蛋白磷脂酰肌醇激酶-蛋白激酶B(PI3K-Akt)等信号通路,从而对Ⅱ型糖尿病发挥调节作用。与α-葡萄糖苷酶的分子对接结果表明,主要活性成分与靶点结合能均小于-9.0 kcal·mol^(-1),具有非常强烈的结合活性。通过体外酶活性试验测得EGCG、槲皮素、山奈酚等7个活性成分对α-葡萄糖苷酶的半抑制浓度为1.11~80.04μmol·L^(-1),抑制效果均优于阿卡波糖,可作为高效α-葡萄糖苷酶抑制剂,是枇杷叶防治Ⅱ型糖尿病的主要活性成分。本研究结果为开发降血糖药物提供了研究思路。To explore the mechanism of Eriobotrya japonica in the prevention and treatment of type 2 diabetes,Network pharmacology and molecular docking technology were used to explore the common target of loquat leaf and type 2 diabetes.In this study,TCMSP,Uniprot,Genecards,Venny,DAVID and other databases were used to map the interaction network and perform GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes)enrichment analysis.The molecular docking was verified by autodock tools.19 ingredients and 294 related targets were collected from TCMSP datebase,then 89 common targets of type 2 diabetes and loquat leaf active components were obtained in Venny 2.1.0,corresponding to 10 active substances such as EGCG,quercetin,kaempferol andβ-sitosterol.Then the‘active ingredient-disease target’network map was constructed.The results indicated that the active components of loquat leaves regulated type 2 diabetes through regulating oxidative stress response,serine/threonine kinase activity,responding to lipopolysaccharide and epithelial cell proliferation,then regulating AGE-RAGE(Advanced glycation end products and the receptor for advanced glycation end products),HIF-1(Hypoxia inducible factor-1)and PI3 K-Akt(Phosphatidylinositol 3 Kinase-protein kinase B)signaling pathways.The molecular docking results showed that the binding energy of the main active components onα-glucosidase was less than-9.0 kcal·mol^(-1),which had very strong binding activity.The semi-inhibitory concentrations of 7 active ingredient such as EGCG,quercetin and kaempferol onα-glucosidase were in the range of 1.11~80.04μmol·L^(-1),as measured by in vitro enzyme activity assay.The inhibitory effects were better than those of acarbose,which can be used as efficientα-glucosidase inhibitor as the main active ingredient of loquat leaf in the prevention and treatment of type 2 diabetes.This study investigated the mechanism of active ingredients of loquat leaf on the prevention and treatment of type II diabetes,and provided research ideas for the

关 键 词：枇杷叶 Ⅱ型糖尿病 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]