基于网络药理学研究玄参治疗糖尿病的作用机制

Mechanism of Scrophulariae in treating diabetes based on network pharmacology

目的通过网络药理学的方法探讨玄参治疗糖尿病的作用机制。方法2022年1月至2023年1月,通过中药系统药理学数据库与分析平台(TCMSP)获取玄参的主要活性成分及其作用靶点,人类基因综合数据库(Genecards)、人类在线孟德尔遗传数据库(OMIM)、治疗靶点数据库(TTD)获取糖尿病相关靶点;玄参和糖尿病靶点取交集获得玄参-糖尿病交集靶点。利用STRING和DAVID数据库构建蛋白质-蛋白质相互作用(PPI)网络并进行基因本体(GO)富集分析、京都基因和基因组数据库(KEGG)富集分析,微生信进行可视化。用分子对接的方法来模拟核心靶点与活性成分的结合强度。结果玄参治疗糖尿病的主要活性成分有β-谷甾醇、谷甾醇、柳杉酚、哈巴俄苷、14-去氧-12(R)-磺酸基穿心莲内酯5种,与糖尿病的交集靶点有前列腺素内过氧化物合酶2(PTGS2)、乙酰胆碱酯酶(ACHE)、β2肾上腺素受体(ADRB2)等14个。GO分析结果显示,玄参-糖尿病交集靶点的生物过程主要有脂多糖反应,细胞组分主要在质膜,分子功能主要有过氧化物酶的活性。KEGG分析结果显示,玄参治疗糖尿病的信号通路主要有脂肪细胞内脂类分解的调节和癌症通路等。分子对接结果显示β-谷甾醇与糖原合成酶激酶(GSK-3β)、14-去氧-12(R)-磺酸基穿心莲内酯与PTGS2、柳杉酚与GSK-3β结合更为紧密。结论玄参可能通过作用于PTGS2、GSK-3β、ACHE等靶点,调节脂类分解,从而发挥治疗糖尿病的作用。该研究初步揭示了玄参治疗糖尿病的多成分、多靶点、多通路的作用机制,为后续玄参治疗糖尿病的机制提供了研究思路。

Objective To investigate the mechanism of treating diabetes with Scrophulariae through network pharmacology.Meth⁃ods From January 2022 to January 2023,the main active constituents and their targets of Scrophulariae were obtained from the Traditional Chinese Medicine Pharmacology Database and Analysis Platform(TCMSP),and the diabetes related targets were obtained from GeneCards,Online Mendelian Inheritance in Man(OMIM)and Therapeutic Target Database(TTD).The intersection of Scrophulariae and diabetes targets was obtained.STRING and DAVID databases were used to construct protein-protein interaction(PPI)network,GO enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis were carried out,with visualization via microbioinformatics.Molecular docking was used to simulate the binding strength of the core target to the active component.Results Scrophularia ningpoensis,which is used to treat diabetes,contains five main active ingredients,includingβ-sitosterol,sitosterol,taxifolin,haboside,and 14-deoxygenation-12(R)-sulfonate-based Andrographolide.It had 14 overlapping targets with diabetes,including prostaglandin-endoperoxide synthase 2(PTGS2),acetylcholinesterase(ACHE),and theβ2-adrenergic receptor(ADRB2).The results of GO analysis showed that the biological processes at the intersection target of Scrophularian-diabetes mainly included lipopolysaccharide reaction,the cell components were mainly in the plasma membrane,and the molecular functions mainly contained peroxidase activity.KEGG analysis results showed that the signaling pathways of Scrophulariae in the treatment of diabetes mainly included the regulation of lipid decomposition in adipocytes and the cancer pathway.Molecular docking results showed thatβ-sitosterol and glycogen synthase kinase(GSK-3β),14-deoxy12(R)-sulfonyl andrographolide and PTGS2,and tomerol and GSK-3βwere more closely bound.Con⁃clusions Scrophulariae may regulate lipidysis by acting on PTGS2,GSK-3β,ACHE and other targets,thus playing a role in the treatment of diabetes.This study initially revealed the multi-component,multi-target and multi-pathway mechanism of Scrophulariae in the treatment of diabetes,and provided ideas for the subsequent researches on mechanism of Scrophulariae in the treatment of diabetes.