高等学校化学学报 ›› 2015, Vol. 36 ›› Issue (10): 1894-1899.doi: 10.7503/cjcu20150307

• 分析化学 • 上一篇    下一篇

液相色谱-质谱联用技术结合多探针底物法研究人参皂苷Rb1的体外代谢

王一博1, 肖丹2,3, 李晓宇1, 戴雨霖1, 越皓1(), 刘淑莹1,3   

  1. 1. 长春中医药大学吉林省人参科学研究院, 长春130117
    2. 长春工业大学化学工程学院, 长春130012
    3. 中国科学院长春应用化学研究所, 长春质谱中心, 长春130022
  • 收稿日期:2015-04-16 出版日期:2015-10-10 发布日期:2015-09-14
  • 作者简介:联系人简介: 越 皓, 男, 博士, 研究员, 主要从事天然产物质谱及活性筛选方面的研究. E-mail:jlsrskxyjy@126.com;刘淑莹, 女, 博士, 教授, 博士生导师, 主要从事有机质谱方面的研究. E-mail:liusy@ciac.jl.cn
  • 基金资助:
    吉林省科技发展计划(批准号: 20130303101YY)和公益性行业(农业)专项(批准号: 20130311106)资助

Metabolism of Ginsengside Rb1 in Rat Liver Microsomal in vitro by HPLC-MS and Cocktail Probe Substrats Method

WANG Yibo1, XIAO Dan2,3, LI Xiaoyu1, DAI Yulin1, YUE Hao1,*(), LIU Shuying1,3,*   

  1. 1. Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China
    2. Chemical Engineering Institute, Changchun University of Technology, Changchun 130012, China
    3. Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry,Chinese Academy of Sciences, Changchun 130022, China
  • Received:2015-04-16 Online:2015-10-10 Published:2015-09-14
  • Contact: YUE Hao,LIU Shuying E-mail:jlsrskxyjy@126.com

摘要:

以奥美拉唑、 苯妥英、 卡马西平和非那西丁为检测肝药酶细胞色素P450酶(CYP450)亚型的专属探针药物, 通过原型药物减少量测定法考察药物体外代谢的变化, 评价人参皂苷Rb1对CYP450不同亚型酶的作用. 结果表明, P2C9, P2C19和P3A4实验组与对照组差异不显著, P1A2实验组与对照组差异显著, 表明人参皂苷Rb1能诱导P1A2亚型酶的活性, 促进底物与酶反应, 加快底物的代谢, 而对P2C9, P2C19和P3A4三个亚型酶有弱的诱导或无诱导作用. 根据快速分离液相色谱-质谱联用(RRLC-MS/MS)检测结果推断, 人参皂苷Rb1在CYP450酶中的代谢产物可转化为人参皂苷Rb1氧化产物(Rb1+O)及人参皂苷Rd和F2.

关键词: 人参皂苷Rb1, 细胞色素P450酶, 液相色谱-质谱联用, 体外代谢

Abstract:

The effect and metabolisms of ginsenoside Rb1 were studied on cytochrome P450s(CYP450). The induction or inhibition effects of CYP450 enzymes were evaluated by investigating the changes of probe drug in concentration. The metabolites of ginsenoside Rb1 including ginsenoside Rd, ginsenoside F2 and the oxidation of ginsenoside Rb, were found and identified in CYP450 enzyme with RRLC-MS/MS. The difference between the experimental group and control group was not significant except CYP1A2 group, indicating that ginsenoside Rb1 has more induced effect to the CYP1A2 group than the others. Ginsenoside Rb1 promoted reaction and speed up the metabolism of probe drug. The method can effectively and easily analyze the impact on the enzyme and possible metabolites.

Key words: Ginsenoside Rb1, Cytochrome P450 enzyme, Liquid chromatogram-mass spectrum(LC-MS), Metabolism in vitro(Ed.: N, K)

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