title: Identification of Human UDP-Glucuronosyltransferase 1A4 as the Major Isozyme Responsible for the Glucuronidation of 20(S)-Protopanaxadiol in Human Liver Microsomes.
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.
authors.affiliation: Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210038, China. lisa02252@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210038, China. 13764556163@126.com.
authors.forename: Chunyong
authors.initials: C
authors.lastname: He
authors.affiliation: 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. lianxiang1205@163.com.
authors.forename: Lianxiang
authors.initials: L
authors.lastname: Fang
authors.affiliation: 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. yl7@shutcm.edu.cn.|Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China. yl7@shutcm.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210038, China. ztwang@shutcm.edu.cn.|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. ztwang@shutcm.edu.cn.|Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China. ztwang@shutcm.edu.cn.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D036145:Ginsenosides / Q000378:metabolism*; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D012502:Sapogenins / Q000378:metabolism*; D014530:Uridine Diphosphate / Q000378:metabolism
chemical_list: D036145:Ginsenosides; D020719:Glucuronides; D007527:Isoenzymes; D012502:Sapogenins; C507965:ginsenoside 20S-protopanaxatriol; D014530:Uridine Diphosphate; D014453:Glucuronosyltransferase
keywords: 20(S)-protopanaxadiol; UGT1A4; glucuronidation; liquid chromatography-mass spectrometry (LC-MS); liver microsomes