鉴定人尿苷二磷酸葡萄糖醛酸基转移酶1A4为负责20(S)-原人参二醇在人肝微粒体中葡萄糖醛酸化的主要同工酶。
Identification of Human UDP-Glucuronosyltransferase 1A4 as the Major Isozyme Responsible for the Glucuronidation of 20(S)-Protopanaxadiol in Human Liver Microsomes.
作者信息
Li Jia, He Chunyong, Fang Lianxiang, Yang Li, Wang Zhengtao
机构信息
Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210038, China.
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.
出版信息
Int J Mol Sci. 2016 Mar 9;17(3):205. doi: 10.3390/ijms17030205.
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.
20(S)-原人参二醇（PPD）是人参皂苷的代表性苷元之一，具有广泛的药理活性。尽管对其I相代谢已进行了广泛研究，但关于该化合物II相代谢的信息仍有待阐明。在此，通过核磁共振光谱和高分辨率质谱明确鉴定出在人肝微粒体（HLM）和大鼠肝微粒体（RLM）中PPD的一种葡萄糖醛酸化代谢产物为PPD-3-O-β-D-葡萄糖醛酸苷。化学抑制和重组人尿苷二磷酸葡萄糖醛酸转移酶（UGT）同工型分析表明，HLM中PPD的葡萄糖醛酸化主要由UGT1A4催化，而UGT1A3显示出较弱的催化活性。总之，首次鉴定出PPD-3-O-β-D-葡萄糖醛酸苷是HLM中PPD的主要葡萄糖醛酸化代谢产物，其由UGT1A4催化。
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