UPLC-Q-Orbitrap-MS结合网络药理学探讨当归四逆汤治疗关节炎及痛经“异病同治”机制分析  

Mechanism of Danggui Sini decoction in treating arthritis and dysmenorrhea disease based on network pharmacology and UPLC-Q-Orbitrap-MS

作　　者：储烟阗 匡艳辉[1] 严曾豪 王德勤[1] 郭海彪[1] 张偲偲 刘晓秋 CHU Yantian;KUANG Yanhui;YAN Zenghao;WANG Deqin;GUO Haibiao;ZHANG Sisi;Liu Xiaoqiu(Guangzhou Baiyunshan Hutchison Whampoa Chinese Medicine Co.,Ltd.,Guangdong 510000,China)

机构地区：[1]广州白云山和记黄埔中药有限公司现代中药研究院,510000 [2]沈阳药科大学中药学院

出　　处：《环球中医药》2023年第8期1526-1541,共16页Global Traditional Chinese Medicine

基　　金：国家科技部重大新药创制(2018ZX09721-004)。

摘　　要：目的基于超高效液相色谱串联四级杆-静电场轨道阱高分辨质谱技术(UPLC-Q-Orbitrap-MS)结合网络药理学探究当归四逆汤治疗类风湿性关节炎及原发性痛经“异病同治”的活性成分及作用机制。方法UPLC-Q-Orbitrap-MS技术对经典名方当归四逆汤的化学成分定性分析。采用中药系统药理学数据库与分析平台(TCMSP)、SwissTargetPrediction数据库对鉴别的化学成分预测靶点;采用Drugbank、OMIM、Genecard数据库收集与类风湿性关节炎、原发性痛经相关的靶点;利用Cytoscape3.7.2软件构建“活性成分—靶点—疾病”网络并分析关键成分和靶点;利用Metascape3.5在线对潜在靶点进行基因本体论功能注释(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路分析。结果共筛选出当归四逆汤治疗类风湿性关节炎及原发性痛经交集靶点96个,筛选出25个核心靶点,富集结果分析显示,990个涉及生物过程、73个涉及细胞组分、100个涉及分子功能。结论结果表明,当归四逆汤可能通过布雷非德菌素A、木犀草素-7-葡萄糖苷、咖啡酸、甘草素等成分作用于酪氨酸激酶(sarcoma gene,SRC)、信号转导子和转录激活子3(signal transducer and activator of transcription 3,STAT3)、表皮生长因子受体(Epidermal growth factor receptor,EGFR)、丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、磷酸肌醇3激酶的p110α催化亚基(phosphatidylinositol-4,5-bisphosphate 3-kinase,PIK3CA)、白介素-6(interleukin-6,IL-6)、花生四烯酸等信号通路发挥抗炎镇痛作用。Objective To investigate the active ingredients and mechanism of action of the classical formula Danggui Sini decoction in the treatment of rheumatoid arthritis and primary dysmenorrhea based on UPLC-Q-Orbitrap-MS.Methods The chemical components of the classical formula Danggui Sini decoction were qualitatively analyzed by UPLC-Q-Orbitrap-MS.The TCM Systematic Pharmacology Database and Analysis Platform(TCMSP)and SwissTargetPrediction database were used for target prediction of the chemical components obtained from the identification;Drugbank,OMIM and Genecard database were used to collect the targets related to rheumatoid arthritis and primary dysmenorrhea;Cytoscape 3.7.2 software was used to construct“active ingredient-potential target-disease”network and analyze key ingredients and key targets;Metascape 3.5 was used to perform online gene ontology(GO)functional annotation and kyoto encyclopedia of genes and genomes(KEGG)pathway analysis on potential targets.The potential targets were screened online using Metascape3.5.Results A total of 96 intersecting targets were screened for Danggui Sini decoction in the treatment of rheumatoid arthritis and primary dysmenorrhea,and 25 core targets were screened.Analysis of the enrichment results showed that 990 involved biological processes,73 involved cellular components,and 100 involved molecular functions.Conclusion The results suggest that Danggui Sini decoction may act on core targets such as SRC,STAT3,EGFR,MAPK1,PIK3CA,IL-6 through Brefeldin A,Luteolin-7-glucoside、Caffeic acid、Liquiritigenin and other components regulates PI3K-Akt,AGE-RAGE,arachidonic acid and other signaling pathways to exert anti-inflammatory and analgesic effects.

关 键 词：当归四逆汤 超高效液相色谱串联四级杆—静电场轨道阱高分辨质谱 网络药理学 类风湿性关节炎 原发性痛经 

分 类 号：R285[医药卫生—中药学]