Science China Life Sciences

, Volume 60, Issue 2, pp 215–224 | Cite as

In vitro and in vivo evaluation of cucurbitacin E on rat hepatic CYP2C11 expression and activity using LC-MS/MS

  • Jian Lu
  • TongGui Ding
  • Xuan Qin
  • MingYao Liu
  • Xin Wang
Open Access
Research Paper


This study explored the effects of cucurbitacin E (CuE), a bioactive compound from Cucurbitaceae, on the metabolism/pharmacokinetic of tolbutamide, a model CYP2C9/11 probe substrate, and hepatic CYP2C11 expression in rats. Liquid chromatography-(tandem) mass spectrometry (LC-MS/MS) assay was used to detect tolbutamide as well as 4-hydroxytolbutamide, and then successfully applied to the pharmacokinetic study of tolbutamide in rats. The effect of CuE on CYP2C11 expression was determined by western blot. CuE (1.25–100 μmol L−1) competitively inhibited tolbutamide 4-hydroxylation (CYP2C11) activity only in concentration-dependent manner with a K i value of 55.5 μmol L−1 in vitro. In whole animal studies, no significant difference in metabolism/pharmacokinetic of tolbutamide was found for the single pretreatment groups. In contrast, multiple pretreatments of CuE (200 μg kg−1 d−1, 3 d, i.p.) significantly decreased tolbutamide clearance (CL) by 25% and prolonged plasma half-time (T 1/2) by 37%. Moreover, CuE treatment (50–200 μg kg−1 d−1, i.p.) for 3 d did not affect CYP2C11 expression. These findings demonstrated that CuE competitively inhibited the metabolism of CYP2C11 substrates but had no effect on rat CYP2C11 expression. This study may provide a useful reference for the reasonable and safe use of herbal or natural products containing CuE to avoid unnecessary drug-drug interactions.


cucurbitacin E CYP2C11 LC-MS/MS pharmacokinetic tolbutamide 



This work was supported by the National Natural Science Foundation of China (81301908), and the Science and Technology Commission of Shanghai Municipality (13ZR1412600, 14DZ2270100).


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© The Author(s) 2016

Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Authors and Affiliations

  • Jian Lu
    • 1
  • TongGui Ding
    • 1
  • Xuan Qin
    • 1
  • MingYao Liu
    • 1
  • Xin Wang
    • 1
  1. 1.Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghaiChina

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