基于网络药理学探究达原饮治疗儿童新型冠状病毒肺炎引起发热的作用机制

Mechanism of Dayuanyin(达原饮)in the treatment of fever caused by children with corona virus disease 2019 based on network pharmacology

目的基于网络药理学的方法,探讨达原饮治疗儿童新型冠状病毒肺炎(COVID-19)引起发热的作用机制。方法通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform, TCMSP)和中药分子机制的生物信息学分析工具(a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine, BATMAT-TCM)数据库检索获取达原饮的有效中药成分和靶点,通过美国国立生物技术信息中心(national center for biotechnology information, NCBI)、在线人类孟德尔遗传数据库(online mendelian inheritance in man, OMIM)、比较毒物基因组学数据库(the comparative toxicogenomics database, CTD)、治疗靶标数据库(therapeutic target database, TTD)检索疾病"fever"得到发热相关靶点。对二者进行比较分析,取重复值,得到达原饮治疗发热的相关靶点,通过R语言对达原饮治疗发热的靶点进行基因本体(gene ontology, GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)富集分析。结果得到达原饮活性成分254个,靶点1733个;得到发热靶点377个;取重复值得到达原饮治疗COVID-19引起的发热靶点135个;筛选之后得到关键靶点24个;GO富集得到1895条,其中生物过程1870条,细胞组成14条,分子功能11条;KEGG富集得到114条信号通路。结论达原饮可能通过白介素-1β(IL-1β)、白介素-6 (IL-6)、白介素-10 (IL-10)、肿瘤坏死因子-α(TNF-α)、血管内皮生长因子(VEGF)、白介素-4 (IL-4)、CXC趋化因子配体8 (CXCL8)、CC趋化因子配体-2 (CCL2)、纤维连接蛋白抗体(FN1)、Toll样受体-4 (TLR4)、转化生长因子β1 (TGFβ1)、胰岛素样生长因子-1 (IGF1)、白介素-13 (IL-13)、肿瘤抑制因子P53 (TP53)、细胞间黏附分子-1 (ICAM1)、半胱天冬氨酸蛋白酶-3 (CASP3)、超氧化物歧化酶-2 (SOD2)、丝裂原活化蛋白激酶-1 (MAPK1)、一氧化氮合酶-2 (NOS2)、CXC家族趋化因子受体-4 (CXCR4)、C-反应蛋白(CRP)、前列腺素内过氧化物合酶-2 (PTGS2)、谷丙转氨酶(GPT)、窖蛋白-1 (CAV1)多个靶点作用于糖基化终末产物-糖基化终末产物受体(AGE-RAGE)信号通路、肿瘤坏死因子(TNF)信号通路、白介素-17 (IL-17)信号通路等多条信号通路,发挥抗炎及解热作用。

Objective To explore the mechanisms of Dayuanyin(达原饮) in the treatment of fever caused by children with corona virus disease 2019(COVID-19) based on network pharmacology.Methods The effective Chinese materia medica(CMM) components and targets of Dayuanyin were obtained by database retrieval of traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) and a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine(BATMAT-TCM).Fever-related targets were obtained by retrieval of the disease "fever" through national center for biotechnology information(NCBI),online mendelian inheritance in man(OMIM),the comparative toxicogenomics database(CTD),and therapeutic target database(TTD).After comparing and analyzing the two,the duplicate values were used to obtain the target of treating fever with Dayuanyin.The enrichment analysis of gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) was carried out by R language of the target of treatment of fever by Dayuanyin.Results We obtained 254 active ingredients and 1733 targets of Dayuanyin;obtained 377 feverish targets;135 fever targets caused by COVID-19 were achieved by duplicate values of treating fever with Dayuanyin;24 key targets were obtained after screening;1895 results were obtained by enrichment of GO,including 1870 biological processes,14 cell compositions,and 11 molecular functions;114 signaling pathways were obtained by KEGG enrichment.Conclusion Dayuanyin may act on multiple signal pathways such as advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway,tumor necrosis factor(TNF) signaling pathway,IL-17 signaling pathway through multiple targets such as interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),vascular endothelial growth factor(VEGF), interleukin-4(IL-4), C-X-C motif chemokine ligand 8(CXCL8), C-C motif chemokine ligand 2(CCL2), fibronectin antibody1(FN1),toll-like receptor-4(TLR4),transforming growth factor-β1(TGFβ1),insulin-like growth factor1(IGF1), interleukin-13(IL-13),tumor-inhibiting factor P53(TP53),intercellular adhesion molecule-1(ICAM1),caspase-3(CASP3), superoxide dismutase-2(SOD2),mitogen-activated protein kinase-1(MAPK1), nitric oxide synthase-2(NOS2),C-X-C chemokine receptor type-4(CXCR4),C-reactive protein(CRP),prostaglandin-endoperoxide synthase-2(PTGS2),glutamic-pyruvic transaminase(GPT) and caveolin-1(CAV1) to exert the function of anti-inflammatory and antipyretic.