藏药麻花秦艽防治细胞因子风暴活性成分与作用机制的网络药理学研究  

Active components and mechanism of Tibetan medicine Gentiana straminea against cytokine storm

作　　者：高小敏 徐雅 刘杜霞 张晓英 李捷[1] 仝敏 赵勤 GAO Xiao-min;XU Ya;LIU Du-xia;ZHANG Xiao-ying;LI Jie;TONG Min;ZHAO Qin(Engineering Research Center of Tibetan Medicine Testing Technologyof Ministry of education,Tibetan Medicine Screening Laboratory,School of Medicine,Tibet University for Nationalities,Xianyang 712082,China)

机构地区：[1]西藏民族大学藏药检测技术教育部工程研究中心,西藏民族大学医学院藏药筛选实验室,陕西咸阳712082

出　　处：《中草药》2021年第1期186-195,共10页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81660722);西藏民族大学新冠肺炎疫情应急项目(XZMDYJ02);西藏民族大学重点项目(13myZP07);陕西省中医管理局(2019-ZZ-JC046)。

摘　　要：目的应用网络药理学方法对藏药麻花秦艽防治细胞因子风暴的主要活性成分及可能作用机制进行预测分析。方法通过中药系统药理学数据库分析平台(TCMSP)及人类基因(GeneCards)数据库收集麻花秦艽的活性化合物和与细胞因子风暴相关靶点;应用Cytoscape 3.6.1软件构建麻花秦艽活性成分-细胞因子风暴靶点调控网络图;构建蛋白-蛋白相互作用网络图筛选核心靶点,利用DAVID在线数据库对核心蛋白进行基因本体论(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果筛选得到麻花秦艽与防治细胞因子风暴相关的14个活性化合物和31个有效靶点,核心化合物和靶点分别为熊果酸、木犀草素、山柰酚、豆甾醇、β-谷甾醇和白细胞介素6(interleukin-6,IL-6)、信号转导子与转录激活子3(signal transducers and transcriptional activators 3,STAT3)、c-Jun氨基末端激酶(C-jun amino-terminal kinase,JNK)、蛋白激酶B1(protein kinase B1,Akt1)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、基质金属蛋白酶(matrix metallopeptidase 9,MMP9)、血管内皮生长因子(vascular endothelial growth factor A,VEGF)、IL-1β、IL-10等。GO分析发现麻花秦艽在抗细胞因子风暴时主要涉及调控细胞凋亡、基因表达、细胞因子活性、一氧化氮生物合成过程的正调控、生长因子活性、免疫应答等过程。KEGG通路分析发现其主要涉及细胞因子风暴相关通路T细胞受体信号通路、酪氨酸激酶JAK和转录因子STAT(Januskinase-signaltransducerandactivatorof transcription,Jak-STAT)信号通路、低氧诱导因子1(hypoxia-inducible factor 1,HIF-1)信号通路、肿瘤坏死因子信号通路、Toll样受体信号通路、磷酸化磷酯酰肌醇3激酶(phosphatidylinositide 3-kinases,PI3K)-Akt信号通路等核心靶点通路。结论通过网络药理学数据挖掘初步预测了藏药Objective To analyze the main active components and possible mechanism of Mahuaqinjiao(Gentiana straminea)in the preventive treatment of cytokine storm by network pharmacology.Methods The therapeutic targets for cytokine storms and its active ingredients of G.straminea were searched and collected from the database of TCMSP and GeneCards;The regulatory network map of active component cytokine storm targets of G.straminea was constructed by using Cytoscape 3.6.1;The network map of protein-protein interaction was constructed to screen the core target,and the gene ontology(GO)function enrichment analysis and KEGG pathway enrichment analysis of the core protein were carried out by using the online database of DAVID.Results After screening,14 active components and 31 effective targets for prevention and treatment of cytokine storm were obtained,mainly including IL6,STAT3,Jun,AKT1,EGFR,MMP9,VEGFA,IL-1β,IL-10,and other core targets.Go analysis showed that G.straminea mainly involved in the regulation of apoptosis,gene expression,cytokine activity,positive regulation of nitric oxide biosynthesis,growth factor activity,immune response and other processes.KEGG pathway analysis showed that the main pathways related to cytokine storm were T-cell receptor signaling pathway,JAK STAT signaling pathway,HIF-1 signaling pathway,tumor necrosis factor signaling pathway,Toll like receptor signaling pathway,PI3 K Akt signaling pathway and other core target pathways.Conclusion Based on the data mining of network pharmacology,the potential active components and possible mechanism targets of G.straminea against cytokine storm were predicted preliminarily,in order to provide reference for the application of G.straminea in the prevention and control of cytokine storm,and provide ideas for the development of new uses of G.straminea.

关 键 词：麻花秦艽 细胞因子风暴 高细胞因子血症 新型冠状病毒肺炎 网络药理学 熊果酸 木犀草素 山柰酚 豆甾醇 Β-谷甾醇 

分 类 号：R285[医药卫生—中药学]