高等学校化学学报

高等学校化学学报 ›› 2013, Vol. 34 ›› Issue (5): 1067.doi: 10.7503/cjcu20130107

• 分析化学 • 上一篇    下一篇

UPLC-MS/MS结合多探针底物方法研究刺五加叶中黄酮苷类成分对CYP450活性的影响

毕云枫1,2, 朱洪彬1, 皮子凤1, 刘志强1, 宋凤瑞1   

  1. 1. 中国科学院长春应用化学研究所化学生物学实验室, 长春质谱中心, 长春 130022;
    2. 吉林农业大学食品科学与工程学院, 长春 130118
  • 收稿日期:2013-01-30 出版日期:2013-05-10 发布日期:2013-05-10
  • 通讯作者: 宋凤瑞, 女, 博士, 研究员, 博士生导师, 主要从事天然产物质谱及代谢方面的研究. E-mail: songfr@ciac.jl.cn E-mail:songfr@ciac.jl.cn
  • 基金资助:

    国家自然科学基金(批准号: 81073040)及国家博士后基金(批准号: 2011M500625)资助.

Effects of Flavonoides from the Leaves of Acanthopanax on the Activity of CYP450 Isozymes in Rat Liver Microsomes by a UPLC-MS/MS and Cocktail Probe Substrates Method

BI Yun-Feng1,2, ZHU Hong-Bin1, PI Zi-Feng1, LIU Zhi-Qiang1, SONG Feng-Rui1   

  1. 1. Chemical Biology Laboratory, Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China;
    2. College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China
  • Received:2013-01-30 Online:2013-05-10 Published:2013-05-10
  • Contact: SONG Feng-Rui E-mail:songfr@ciac.jl.cn

PDF (PC)

被引次数

15

摘要：

利用超高效液相色谱-串联质谱联用(UPLC-MS/MS)的多反应监测(MRM)技术结合多探针底物方法, 研究了刺五加叶中的主要黄酮苷类化合物槲皮苷、金丝桃苷及芦丁对肝细胞色素P450酶(CYP450)亚型CYP1A2, CYP2C, CYP2E1, CYP2D和CYP3A活性的影响. 结果表明, 3种化合物对各CYP亚型酶均有抑制作用, 其中金丝桃苷和槲皮苷对CYP1A2催化的非那西丁的O-脱乙基反应抑制的IC50值分别为46.53和49.75 μmol/L, 金丝桃苷和芦丁对CYP2E1催化的氯唑沙宗的6-羟基化反应抑制的IC50值分别为99.87和86.36 μmol/L. 机理性抑制实验结果表明, 3种化合物对2种亚型酶的抑制作用是随着预孵时间延长而增强的机理性抑制.

关键词: 刺五加叶, 黄酮苷, 肝细胞色素P450酶(CYP450), 超高效液相色谱-串联质谱联用

Abstract:

Effects of flavonoides including quercitrin, hyperoside and rutin from the leaves of Acanthopanax on the activity of hepatic microsomal CYP450 isozymes(CYP1A2, CYP2C, CYP2E1, CYP2D and CYP3A) in rat liver microsomes were analyzed by a ultra performance liquid chromatography-tandem mass spectrometry(multiple reaction monitoring)[UPLC-MS/MS(MRM)] combined with cocktail probe substrates method. The results showed that three compounds on the activities of some CYP450 isozymes were the inhibitory effects using rat liver microsomes, in which the IC50 values of quercitrin and hyperoside to the inhibition of rat microsomal CYP1A2 activity were 46.53 and 49.75 μmol/L, respectively, the IC50 values of hyperoside and rutin for the inhibition of CYP2E1 activity were 99.87 and 86.36 μmol/L, respectively. Mechanism of inhibition experimental results show that three compounds on each CYP450 isozymes inhibiting ability was increased with the increasing of the preincubation time, therefore, the inhibitory effects was a mechanism-based inhibition.

Key words: Leaves of Acanthopanax, Flavonoides, Cytochrome P450, Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)

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