甘草中黄酮类化合物的网络药理学研究

目的:分析、预测甘草中黄酮类化合物的潜在药理作用及可能作用机制。方法:采用网络药理学方法,依据中药整合药理学计算平台(TCMSP)等数据库,以化合物的口服药物生物利用度(OB)>30%和类药性(DL)>0.18为标准,筛选甘草中的黄酮类化合物。采用药效团匹配与PharmMapper数据库预测其潜在的作用靶点,随后借助生物学信息注释数据库V6.8(DAVIDV6.8)分析工具对获得的靶点蛋白进行京都基因与基因组数据库(KEGG)信号通路分析和基因本体(GO)生物过程富集分析(以P<0.05为标准判断相关),并运用Cytoscape3.5.1软件构建甘草中黄酮类化合物-靶点蛋白-信号通路网络图。结果:共从甘草中筛选出了19个黄酮类化合物(如甘草苷、异甘草苷、甘草素等),涉及细胞视黄酸结合蛋白2、脑啡肽酶等78个靶点蛋白(共188次),以及胰岛素信号通路、磷脂酰肌醇3激酶-丝氨酸/苏氨酸激酶(PI3K-Akt)等40条信号通路(其中与癌症相关的通路8条、与内分泌系统相关的通路7条、与信号转导相关的通路6条、与传染病相关的通路5条、与代谢相关的通路3条等);所建黄酮类化合物-靶点蛋白-信号通路网络图显示,甘草中黄酮类化合物可通过多个靶点作用于不同的疾病代谢通路。结论:甘草中黄酮类化合物对癌症、内分泌系统、传染病、代谢系统等方面疾病可能具有治疗作用,且可能有潜在的抗帕金森症作用。

Research on Network Pharmacology of Flavonoids from Glycyrrhiza uralensis

OBJECTIVE: To analyze and predict potential pharmacological effects and mechanism of flavonoids from Glycyrrhiza uralensis. METHODS:By the means of network pharmacology,according to TCM integrative pharmacology platform (TCMSP),using oral bioavailability(OB)>30% and drug-likeness(DL)>0.18 of compound as reference,flavonoids compound of G. uralensis were screened. The potential targets of flavonoids were predicted with pharmacophore matching and PharmMapper date base. DAVID V 6.8 analysis tool was used for KEGG signaling pathway analysis and GO biological process enrichment analysis(using P<0.05 as judgement standard)of target protein. A flavonoids-targets-signaling pathways network was built through Cytoscape 3.5.1 software. RESULTS:A total of 19 flavonoids compounds(such as liquiritin,isoliquiritin and liquiritigenin,etc.) were screened,involving 78 target proteins as cellular retinoic acid-binding protein 2 and neprilysin(188 times in total),40 signaling pathways(among them,8 pathways related to cancer,8 pathways related to endocrine system,6 pathways related to signal transduction,5 pathways related to infectious diseases and 3 pathways related to metabolism)as insulin signaling pathway, PI3K-Akt and so on. The flavonoids-targets-signaling pathways network model showed that flavonoids compounds of G. uralensis could act on different metabolic pathways through multiple targets. CONCLUSIONS:The flavonoids of G. uralensis have therapeutic effect on diseases of cancer,endocrine system,infectious diseases,metabolism and so on. It may have potential anti-parkinson’s effect.