丁欣,张雅,白敏,龙翠萍,张星星,谭光国,唐于平,周倩
DING Xin,ZHANG Ya,BAI Min,LONG Cuiping,ZHANG Xingxing,TAN Guangguo,TANG Yuping,ZHOU Qian

• 1:陕西中医药大学药学院
• 2:空军军医大学药学系
• 3:空军军医大学西京医院中医科

摘要(Abstract)：

目的 探讨四逆汤治疗脓毒症的活性成分、作用靶点及机制。方法 采用超高效液相色谱-四级杆飞行时间质谱(UHPLC-Q-TOFMS)鉴定四逆汤的潜在活性成分，通过中药系统药理学数据库与分析平台和Swiss Target Prediction数据库预测其作用靶点，GeneCards、GisGeNET和comparative toxicogenomics database (CTD)数据库寻找脓毒症靶点，分别用String平台、Cytoscape 3.8.0软件构建蛋白-蛋白相互作用、成分-靶点-通路网络，筛选活性成分和潜在靶点，借助DAVID数据库对潜在靶点进行基因本体论(gene ontology, GO)注释和基因组百科全书(kyoto encyclopedia of genes and genomes, KEGG)信号通路富集分析，最后采用分子对接、表面等离子共振技术验证成分和靶点之间的结合能力与亲和力。结果 共鉴定出46种潜在活性成分、筛选到156个关键靶点；GO富集得到1 019个条目、151条通路，涉及癌症信号、脂质与动脉粥样硬化等；验证结果显示宋果灵、1-脱氢-8-姜酮、芒柄花黄素等成分与AKT1、TNF、TP53等关键靶点结合良好，宋果灵、芒柄花黄素与AKT的亲和力良好(K_d=4.424×10~(-4)、2.218×10~(-4)mol·L~(-1))。结论 初步探讨了四逆汤治疗脓毒症的作用机制，为进一步研究提供依据。
Objective To explore the active components, targets and mechanism of Sini Decoction(SND) in the treatment of sepsis.Methods The potential active components of SND were identified by UHPLC-Q-TOFMS.Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Swiss target prediction were used to predict their targets.The databases including Genecards, GisGeNET and comparative toxicogenomics database(CTD) were used to find the targets of sepsis.Protein-protein interaction and components-targets-pathways networks were constructed and active components and potential targets were found using String platform and Cytoscape 3.8.0 software, respectively.David database was used to perform gene ontology(GO) annotation and kyoto encyclopedia of genes and genomes(KEGG) metabolic pathway enrich analysis.Finally, molecular docking and surface plasmon resonance were used to verify the binding and affinity between components and targets.Results A total of 46 potential active components were identified and 156 key targets were screened; 1 019 items were found in GO function enrichment analysis, and 151 signal pathways were found, involved in cancer, lipid and atherosclerosis etc.The validation results showed that songorine, 1-dehydro-8-gingerone, formononetin and other components were well bound with key targets such as AKT1,TNF and TP53,and songorine and formononetin had good affinity with AKT(K_d=4.424×10~(-4) mol·L~(-1),K_d=2.218×10~(-4) mol·L~(-1)).Conclusion The mechanism of SND in the treatment of sepsis was preliminarily discussed, which provides a basis for further research.

关键词(KeyWords)： 化学物质组学;四逆汤;脓毒症;网络药理学;分子对接;表面等离子共振
chemomics;sini decoction;sepsis;network pharmacology;molecular docking;surface plasmon resonance

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(82003916/82173772);; 陕西省重点产业创新链项目(2022ZDLSF05-06);; 药物质量与安全预警教育部重点实验室资助项目(DQCP20/21PQ07)

作者(Author): 丁欣,张雅,白敏,龙翠萍,张星星,谭光国,唐于平,周倩
DING Xin,ZHANG Ya,BAI Min,LONG Cuiping,ZHANG Xingxing,TAN Guangguo,TANG Yuping,ZHOU Qian

DOI: 10.14066/j.cnki.cn21-1349/r.2022.0698

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