[关键词]
[摘要]
目的 运用网络药理学的方法探究黄芩抗炎的作用机制。方法 通过中药系统药理学分析平台(TCMSP)数据库搜索黄芩中的成分,结合“类药五原则”与“口服生物利用度>30%”筛选黄芩活性成分。采用PharmMapper网络服务器预测其作用靶点,并采用Cytoscape 3.4.0软件构建黄芩活性成分-预测靶点网络。在TTD数据库中以“Anti-inflammatory”为关键词搜索抗炎靶点,使用String数据库进行蛋白质-蛋白质相互作用分析,构建蛋白质-蛋白质相互作用网络,并将其与活性成分-预测靶点融合,获得黄芩活性成分的抗炎作用靶点。使用DAVID数据库对黄芩抗炎作用靶点进行KEGG通路富集分析,以探究黄芩抗炎的作用机制。结果 获得黄芩中具有类药性、口服吸收良好的28个成分,包括黄芩苷、黄芩素、汉黄芩苷、汉黄芩素等黄酮类成分,表小檗碱、黄连碱等生物碱类成分以及二氢木蝴蝶素等酚类物质。黄芩抗炎作用的主要靶点有丝裂原活化蛋白激酶14(MAPK14)、肿瘤坏死因子受体超家族成员1A(TNFRSF1A)、表皮生长因子受体(EGFR)、E-选择素(SELE)等。其中丹参素、表儿茶素、黄连碱等成分主要作用于MAPK14;红花素等作用于TNFRSF1A;二氢木蝴蝶素A、5,7,4'-三羟基-8-甲氧基黄酮、5,7,4'-三羟基-8-甲氧基黄烷酮、黄芩苷等成分主要作用于EGFR。KEGG分析得到与黄芩抗炎作用有关的通路11条,主要涉及肿瘤坏死因子信号通路、MAPK信号通路等。结论 黄芩中的活性成分主要通过MAPK14、EGFR、TNFRSF1A、SELE等靶点抑制炎症因子的产生、抑制炎症因子与相应受体结合、阻断炎症反应的启动等,最终发挥抗炎效应。
[Key word]
[Abstract]
Objective To explore the anti-inflammatory mechanism of Scutellarlae Radix (SR) by the network pharmacology. Methods Firstly, the components in SR were searched through TCMSP database and screened with "Lipinski rule" and "Oral Bioavailability > 30%" rules。The targets of above components selected by PharmMapper web server and Cytoscape 3.4.0 was used to build a network between components and targets (component-target network, CTN). Secondly, "anti-inflammatory" targets was searched from Therapeutic Target Database (TTD) with keyword "anti-inflammatory", and targets retrieved were used to build a protein-protein interaction (PPI) network based on the analysis by String database. To obtain anti-inflammatory targets of the active components in SR, the PPI network was fused with the CTN. Finally, the DAVID database was used to perform KEGG pathway enrichment analysis in order to explore the anti-inflammatory mechanism of SR. Results Twenty-eight components in SR were obtained, including flavonoids such as baicalin, baicalein, wogonin, wogonoside, etc, alkaloids such as berberine, and epiberberine,and phenols such as dihydromyricetin, etc. Mitogen-activated protein kinase (MAPK14), tumor necrosis factor receptor superfamily 1A (TNFRSF1A), epidermal growth factor receptor (EGFR), and E-selectin (SELE) were the main targets of SR' anti-inflammatory effect. Salvigenin, epicatechin, and astragalusine mainly acted on MAPK14; Carthamidin acted on TNFRSF1A; Dihydromubutin A, 5,7,4'-trihydroxy-8-methoxyflavone, 5,7,4'-trihydroxy-8-methoxyflavanone, baicalin, and other components mainly acted on EGFR. There were 11 KEGG pathways, mainly related to TNF signaling pathways, MAPK signaling pathway, etc. Conclusion There are three main anti-inflammatory mechanisms in SR, which can inhibit the production of inflammatory factors, inhibit the binding of inflammatory factors to their respective receptors, and block the initiation of inflammatory reactions.
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[基金项目]
四川省大学生创新训练项目(201613705079);四川省大学生创业训练项目(201613705091)