基于UPLC-Q-TOF-MS和网络药理学的雷公藤-甘草配伍减毒作用机制研究  

Mechanisms study of attenuation of compatibility of Tripterygium wilfordii Hook.f.and licorice based on network pharmacology and UPLC-Q-TOF-MS

作　　者：王磊 孙杨 孙悦 李嘉晨 刘莹 刘洪庚 刘雪瑞 王玉明[3] WANG Lei;SUN Yang;SUN Yue(Pharmacy Department,The ECO-CITY Hospital of Tianjin Fifth Central Hospital,Tianjin 300467,China;不详)

机构地区：[1]天津市第五中心医院生态城医院药剂科,天津300467 [2]天津市第五中心医院生态城医院科教部,天津300467 [3]天津中医药大学中药学院,天津301617

出　　处：《中国处方药》2024年第12期1-11,共11页Journal of China Prescription Drug

基　　金：天津市滨海新区卫生健康科技项目(2023BWKQ022)。

摘　　要：目的利用超高效液相色谱-四级杆-飞行时间串联质谱(UPLC-Q-TOF-MS)技术分别检测雷公藤单煎液和雷公藤-甘草合煎液中的化学成分,结合网络药理学阐明以甘草配伍降低雷公藤肝毒性的作用机制。方法利用液质联用技术对雷公藤单煎液和雷公藤-甘草合煎液中化学成分进行分析,探究配伍前后化学成分的变化。基于成分分析结果通过中药系统药理学数据库和分析平台(TCMSP),注释、可视化和集成发现的数据库(DAVID),DisGeNet等数据库对其化学成分、成分靶点以及肝损伤靶点进行检索和分析并绘制韦恩图。将共有靶点输入String数据库进行蛋白质-蛋白质相互作用(PPI)网络构建,并通过Cytoscape 3.9.1软件将网络可视化,并筛选出核心治疗靶点。对核心治疗靶点进行基因本体论(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析。结果采用UPLC-QTOF-MS技术鉴定,雷公藤-甘草合煎液与雷公藤单煎液相比有27种成分减少。雷公藤单煎液、雷公藤-甘草合煎液成分与肝损伤相关靶点取交集,分别得到146个和244个共有靶点。通过PPI网络分析发现,肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、酪氨酸激酶(SRC)等靶点可能就是雷公藤造成肝脏损伤的关键靶点,蛋白激酶B1(Akt1)、肿瘤蛋白53(TP53)等靶点可能是雷公藤-甘草配伍减毒降低肝脏损伤的关键靶点。KEGG结果显示晚期糖基化终产物-晚期糖基化终末产物受体(AGE-RAGE)信号通路、脂质和动脉粥样硬化、磷脂酰肌醇3激酶白激酶B(PI3K-Akt)信号通路、丝裂原活化蛋白激酶(MAPK)信号通路和TNF信号通路等信号通路的生物过程可能是雷公藤配伍甘草减毒的起效通路。结论雷公藤-甘草配伍通过多靶点和多通路发挥降低肝毒性的作用。Objective To analyze the chemical constituents in Tripterygium wilfordii Hook.f.single decoction and Tripterygium wilfordii Hook.f.-licorice mixed decoction based on UPLC-Q-TOF-MS technology,aiming to elucidate the mechanism behind licorice's role in reducing the liver toxicity of Tripterygium wilfordii Hook.f.through network pharmacology.Methods Liquid chromatography-mass spectrometry was utilized to analyze the chemical constituents in Tripterygium wilfordii Hook.f.single decoctions and Tripterygium wilfordii Hook.f.-licorice mixed decoction,assessing the variations in chemical profiles before and after the combination.Utilizing the component analysis results,the chemical constituents,constituents related targets,and liver injury-related targets were identified and analyzed via databases like TCMSP,DAVID,and DisGeNet,and a Venn diagram was constructed,and the common targets were entered into the String database to build a PPI network,which was visualized by using Cytoscape software,and the core therapeutic targets were screened for GO and KEGG enrichment analyses.Results Compared to Tripterygium wilfordii Hook.f.single decoction,there were 27 components reduced in the Tripterygium wilfordii Hook.f.-licorice mixed decoction,which was identified by the UPLC-Q-TOF-MS technology.And 146 common targets were obtained from the components of Tripterygium wilfordii Hook.f.single decoction and liver injury,244 common targets were obtained from the components of Tripterygium wilfordii Hook.f.-licorice mixed decoction and liver injury.PPI network analysis identified targets such as TNF,IL-6,and SRC as potential key targets for liver injury caused by Tripterygium wilfordii Hook.f.,Akt1 and TP53 as key targets for mitigating liver injury through the combination of Tripterygium wilfordii Hook.f.and licorice.KEGG analysis demonstrated that the biological processes of the AGERAGE signaling pathway,lipid and atherosclerosis,PI3K-Akt signaling pathway,MAPK signaling pathway,and TNF signaling pathway likely constitute the effectiv

关 键 词：雷公藤 甘草 配伍减毒 成分分析 网络药理学 

分 类 号：R285[医药卫生—中药学]