基于UPLC-MS/MS和分子对接技术考察聚乙二醇400对辛夷挥发油药物动力学与抗炎作用的影响  

Investigation on Pharmacokinetics and Anti-Inflammatory Effects of Polyethylene Glycol 400(PEG)Based on UPLC-MS/MS and Molecular Docking Technology

作　　者：林静琼 郑婕[1] LIN Jingqiong;ZHENG Jie(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong,China)

机构地区：[1]广州中医药大学第一附属医院药学部,广东广州510405

出　　处：《辽宁中医杂志》2023年第12期164-168,I0017,共6页Liaoning Journal of Traditional Chinese Medicine

基　　金：广东省科技计划项目(2011B020310008)。

摘　　要：目的基于超高效液相色谱-串联质谱法(UPLC-MS/MS)和分子对接技术考察聚乙二醇400对辛夷挥发油药物动力学与抗炎作用的影响。方法采取小鼠耳肿胀及足肿胀炎症模型对PEG400与辛夷挥发油共同给药后的抗炎效果进行分析,应用UPLC-MS/MS,以血浆中代谢物桉叶油醇作为关键活性成分,探究肿瘤坏死因子(tumor necrosis factor,TNF)-α、白细胞介素(interleulein,IL)-6、IL-1β、前列腺素E2(PGE2)及核因子(nuclear factor,NF)-κB在内的炎症因子情况,初步分析辛夷挥发油及桉叶油醇的抗炎作用。结果药代动力学研究结果证实,与辛夷挥发油+水组相比,辛夷挥发油+PEG400组中辛夷挥发油与桉叶油醇的AUC0-t别提升2.37、1.98倍,证实PEG400能使辛夷挥发油及桉叶油醇的血药浓度提升;小鼠耳肿胀级足肿胀炎症模型证实小鼠灌胃辛夷挥发油PEG400溶液后抗炎效果升高增强;经多靶点蛋白观察可见辛夷挥发油与桉叶油醇能与TNF-α、IL-6、L-1β、PGE2、NF-κB等多位点结合,应用存在较高亲和力,结合性优于阿司匹林。结论PEG400能够提高辛夷挥发油及桉叶油醇的血药浓度,抗炎能力强,且能与多种炎症因子、靶点蛋白形成氢键,推测可能通过上述因子与辛夷挥发油、桉叶油醇发挥协同作用。Objective To investigate the effect of polyethylene glycol 400(PEG)on the pharmacokinetics and anti-inflammatory effects of the volatile oil of Xinyi(Magnoliae Flos)based on ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)and molecular docking technology.Methods In this study,UPLC-MS/MS was used to investigate the effect of PEG400 on the volatile oil and its major metabolites in rats,and the anti-inflammatory effect of PEG400 combined with volatile oil in mice after ear swelling and foot swelling inflammation model was explored.The plasma metabolite eudesmol was selected as the key active component(ligand),and the inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,prostaglandin E2(PGE2)and nuclear factor(NF)-κB]were selected as the targets.The anti-inflammatory effects of Xinyi(Magnoliae Flos)and eudesmol were preliminarily investigated by molecular docking technology.Results The results of pharmacokinetic study confirmed that AUC0-T scores of Xinyi(Magnoliae Flos)volatile oil and eudesmol in Xinyi(Magnoliae Flos)volatile oil+PEG400 group were increased by 2.37 and 1.98 times,respectively,compared with those in Xinyi(Magnoliae Flos)volatile oil+water group,and it is confirmed that PEG400 could increase the plasma concentrations of Xinyi(Magnoliae Flos)volatile oil and eudesmol.The mouse ear swelling grade foot swelling inflammation model proved that the anti-inflammatory effect increased after instillation of the volatile oil PEG400 solution in mice.According to the observation of multiple target proteins,the volatile oil and eudesmol can bind to TNF-α,IL-6,IL-1β,2PGE2,NF-κB and other sites,with high affinity,and the binding ability was better than aspirin.Conclusion PEG400 can increase the blood concentrations of the Xinyi(Magnoliae Flos)volatile oil and eudesmol,has strong anti-inflammatory ability,and can form hydrogen bonds with a variety of inflammatory factors and target proteins.It is speculated that PEG400 may play a synergistic role with the Xin

关 键 词：UPLC-MS/MS 分子对接技术 聚乙二醇400 辛夷挥发油 药物动力学 抗炎 

分 类 号：R282.7[医药卫生—中药学]