基于血清药物化学和网络药理学的泽漆抗慢阻肺药效物质基础分析  

Analysis on Material Basis of Anti-COPD Effect of Euphorbia helioscopia Based on Serum Pharmacochemistry and Network Pharmacology

作　　者：林丽华 孟晓伟[1] 李家荣[1] 俞洪华 朱清 刘荣华[1] 陈兰英[1] LIN Lihua;MENG Xiaowei;LI Jiarong;YU Honghua;ZHU Qing;LIU Ronghua;CHEN Lanying(Jiangxi University of Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学,南昌330004

出　　处：《中国实验方剂学杂志》2023年第14期150-156,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(82060732);江西省重点研发计划项目(20181ACG70014)。

摘　　要：目的:对泽漆水提物的入血成分进行分析,探讨该水提物抗慢性阻塞性肺疾病(COPD)的药效物质基础。方法:采用超高效液相色谱-四极杆-飞行时间串联质谱法(UPLC-Q-TOF-MS/MS)检测大鼠灌胃泽漆水提物后入血成分,检测条件为Agilent RRHD SB-C_(18)色谱柱(3 mm×100 mm,1.8μm),流动相0.1%甲酸水溶液(A)-乙腈(B)梯度洗脱(0~15 min,5%~30%B;15~20 min,30%~50%B;20~30 min,50%~95%B;30~35 min,95%~5%B),检测波长190~800 nm,柱温40℃,流速0.3 mL·min^(-1),进样量4μL,电喷雾离子源(ESI),正、负离子模式检测,检测范围m/z 50~1 250。利用网络药理学方法对入血成分的靶点与COPD的靶点进行交互分析,通过网络拓扑分析筛选关键成分和关键靶点,运用Metascape数据库预测泽漆抗COPD主要涉及的分子功能、生物过程、细胞组成及信号通路,并采用分子对接技术判断关键靶点与关键成分的亲合力。结果:大鼠灌胃泽漆水提物后,从其含药血清中检测出了29个入血成分,9个为原型成分,20个为代谢产物。网络药理学分析表明木犀草素、槲皮素、芹菜素、柚皮素和helioscopinolide C为泽漆抗COPD的关键成分,血管内皮生长因子A(VEGFA)、白蛋白(ALB)、蛋白激酶B1(Akt1)、肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)为泽漆抗COPD的关键靶点。分子对接结果表明,入血成分中的1个二萜内酯类成分helioscopinolide C和3个黄酮类成分柚皮素、木犀草素、芹菜素与泽漆抗COPD的关键靶点均具有强结合活性。结论:柚皮素、helioscopinolide C、木犀草素、芹菜素可能是泽漆抗COPD的主要药效物质。Objective:To analyze the migrating components in blood of aqueous extract of Euphorbia helioscopia and to explore the pharmacodynamic material basis of aqueous extract of E.helioscopia against chronic obstructive pulmonary disease(COPD).Method:Ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS)was used to detecte the migrating components in blood of rats after intragastric administration of aqueous extract of E.helioscopia.An Agilent RRHD SB-C_(18)(3 mm×100 mm,1.8μm)was used with 0.1%formic acid aqueous solution(A)-acetonitrile(B)as the mobile phase for gradient elution(0-15 min,5%-30%B;15-20 min,30%-50%B;20-30 min,50%-95%B;30-35 min,95%-5%B),and the detection wavelength of 190-800 nm,column temperature of 40℃,flow rate of 0.3 mL∙min-1 and injection volume of 4μL.The electrospray ionization(ESI)was used in positive and negative ion modes,and detection range was m/z 50-1250.Network pharmacological methods were used to screen out the key components and the key targets of COPD through the interaction analysis.Metascape was used to predict the molecular function,biological process,cellular composition and signal pathway involved in the anti-COPD effect of E.helioscopia.Molecular docking technique was used to determine the affinity of key targets and key components.Result:A total of 29 migrating components in blood of rats were identified after intragastric administration of aqueous extract of E.helioscopia,9 of which were prototype components and 20 were metabolites;luteolin,quercetin,apigenin,naringenin and helioscopinolide are the key components of anti-COPD effect of E.helioscopia;Vascular endothelial growth factor A(VEGFA),albumin(ALB),protein kinase B(Akt1),tumor necrosis factor(TNF)and interleukin 6(IL-6)are the key targets of anti-COPD effect of E.helioscopia;one diterpene lactone(helioscopinolide C)and three flavonoids(naringenin,luteolin,apigenin)showed strong binding activity to the key targets of anti-COPD effect of E.helioscopia.Conclusion:Nari

关 键 词：泽漆 慢性阻塞性肺疾病(COPD) 活性成分 血清药物化学 网络药理学 分子对接 超高效液相色谱-四极杆-飞行时间串联质谱法(UPLC-Q-TOF-MS/MS) 

分 类 号：R22[医药卫生—中医基础理论] R28[医药卫生—中医学] R96[理学—分析化学] O657[理学—化学]