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Int. J. Mol. Sci. 2016, 17(3), 205; doi:10.3390/ijms17030205

Identification of Human UDP-Glucuronosyltransferase 1A4 as the Major Isozyme Responsible for the Glucuronidation of 20(S)-Protopanaxadiol in Human Liver Microsomes

1
Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210038, China
2
The Ministry Of Education Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
3
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Chang Won Choi
Received: 16 December 2015 / Revised: 17 January 2016 / Accepted: 26 January 2016 / Published: 9 March 2016
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [2087 KB, uploaded 9 March 2016]   |  

Abstract

20(S)-protopanaxadiol (PPD), one of the representative aglycones of ginsenosides, has a broad spectrum of pharmacological activities. Although phase I metabolism has been investigated extensively, information regarding phase II metabolism of this compound remains to be elucidated. Here, a glucuronidated metabolite of PPD in human liver microsomes (HLMs) and rat liver microsomes (RLMs) was unambiguously identified as PPD-3-O-β-d-glucuronide by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry. The chemical inhibition and recombinant human UDP-Glucuronosyltransferase (UGT) isoforms assay showed that the PPD glucuronidation was mainly catalyzed by UGT1A4 in HLM, whereas UGT1A3 showed weak catalytic activity. In conclusion, PPD-3-O-β-d-glucuronide was first identified as the principal glucuronidation metabolite of PPD in HLMs, which was catalyzed by UGT1A4. View Full-Text
Keywords: UGT1A4; liver microsomes; 20(S)-protopanaxadiol; glucuronidation; liquid chromatography-mass spectrometry (LC-MS) UGT1A4; liver microsomes; 20(S)-protopanaxadiol; glucuronidation; liquid chromatography-mass spectrometry (LC-MS)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Li, J.; He, C.; Fang, L.; Yang, L.; Wang, Z. Identification of Human UDP-Glucuronosyltransferase 1A4 as the Major Isozyme Responsible for the Glucuronidation of 20(S)-Protopanaxadiol in Human Liver Microsomes. Int. J. Mol. Sci. 2016, 17, 205.

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