基于系统药理学分析沙生蜡菊治疗Ⅱ型糖尿病的活性成分预测及机制研究  

Prediction of active constituents and mechanism analysis of Helichrysum arenarium(L.) Moench on anti-typeⅡdiabetes effect based on systematic pharmacology

作　　者：杨金香 朱妍妍 李鸿晔 于利利 陈文[1] 韩博[1] YANG Jinxiang;ZHU Yanyan;LI Hongye;YU Lili;CHEN Wen;HAN Bo(School of Pharmacy,Shihezi University,Shihezi,Xinjiang 832002,China)

机构地区：[1]石河子大学药学院,新疆石河子832002

出　　处：《石河子大学学报（自然科学版）》2021年第2期240-251,共12页Journal of Shihezi University(Natural Science)

基　　金：国家自然科学基金项目(81760756,U1903211),石河子大学成果转化与技术推广计划项目(CGZH201806)。

摘　　要：目的寻找沙生蜡菊抗Ⅱ型糖尿病(T2DM)的活性成分及潜在作用机制。方法采用超高效液相色谱-四极杆串联飞行时间质谱(UPLC-Q-TOF-MS)表征沙生蜡菊中的化学成分,并构建沙生蜡菊化合物数据库。以口服生物利用度(Oral bioavailability,OB)≥30%、类药性(Druglikeness,DL)≥0.18为标准,筛选潜在的活性化合物,并基于随机森林算法和支持向量机算法模型对活性化合物进行靶点预测。通过Cytoscape3.6.1软件绘制沙生蜡菊相互作用网络进行拓扑学分析,结合基因本体(GO)功能富集分析,探讨沙生蜡菊治疗T2DM的作用机制。结果通过UPLCQ-TOF-MS鉴定出沙生蜡菊中的55个化合物,包括29个黄酮、7个酚酸、4个木质素、4个萜类、3个甾体、以及8个其他类化合物。通过药物的吸收、分布、代谢和排泄(ADME)特性筛选出14个活性化合物并预测出34个潜在靶点。根据相互作用网络分析得出沙生蜡菊活性成分主要与雌激素受体1(ESR1)、雄激素受体(AR)、过氧化物酶体增殖物激活受体γ(PPARγ)等靶点有关,与雌激素信号通路、磷脂酰肌醇-3-羟激酶/蛋白激酶B(PI3KAkt)信号通路、胰岛素信号通路等信号通路相关,且34个靶标主要富集于大脑、肝脏及骨骼肌中。GO生物过程富集显示靶点主要参与细胞过程的正调节、生物过程的正调节和细胞代谢过程的正调节等多种生物过程。KEGG通路富集分析结果表明靶标以调节雌激素信号、孕酮介导的卵母细胞成熟、催乳素信号和癌症相关等作用通路发挥对T2DM的治疗作用。结论沙生蜡菊可能通过ESR1、AR和PPARγ等靶点作用于雌激素信号通路、PI3K-Akt信号通路、胰岛素信号通路发挥其药物功效,该工作为阐释沙生蜡菊的化学组成和抗T2DM作用机制提供了有益的参考。Objective To investigate the active components and potential mechanism of anti-T2DM effect of Helichrysum arenarium(L.)Moench.Method The qualitative analysis of chemical constituents of Helichrysum arenarium(L.)Moench was determined by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)and the compound database was built.The ingredient with suitable oral bioavailability values(OB≥30%)and druglikeness index(DL≥0.18)were chosen as the active compounds for further research.Target prediction of active compounds was carried out based on random forest algorithm and support vector machine algorithm model.The Cytoscape 3.6.1 software was used to construct the interaction network for topological analysis,and the mechanism of Helichrysum arenarium(L.)Moench was analysed combined with gene ontology(GO)functional enrichment analysis.Results A total of 55 compounds were identified by UPLC-Q-TOF-MS,including 29 flavonoids,7 phenolic acids,4 lignans,4 terpenoids,3 steroids and 8 other compounds.After ADME screening,14 active ingredients possess favorable pharma cokinetic profiles,which have interactions with 34 potential targets.In addition,via systematic network analyses,the active constituents of Helichrysum arenarium(L.)Moench are mainly related to estrogen receptor 1(ESR1),androgen receptor(AR),and peroxisome proliferator-activated receptor gamma(PPARγ).The major signaling pathways are estrogen signaling pathway,phosphatidylinositol-3-hydroxykinase/protein kinase B(PI3K-Akt)signaling pathway and insulin signaling pathway,etc.The 34 targets are mainly enriched in the heart,liver and skeletal muscle.The enrichment of GO biological processes shows that the target is mainly involved in various biological processes such as positive regulation of cellular process,positive regulation of biological process and positive regulation of cellular metabolic process.After KEGG pathway analysis,it was found that targets were involved in mediating the estrogen signaling pathway

关 键 词：沙生蜡菊 Ⅱ型糖尿病 UPLC-Q-TOF-MS 系统药理学 

分 类 号：R285.5[医药卫生—中药学]