Deglycosylation of Liquiritin Strongly Enhances its Inhibitory Potential Towards UDP-Glucuronosyltransferase (UGT) Isoforms

Authors

  • Bin Guo,

    Corresponding author
    • The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China
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  • Xu-Ran Fan,

    1. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
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  • Zhong-Ze Fang,

    1. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
    2. Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA
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  • Yun-Feng Cao,

    1. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
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  • Cui-Min Hu,

    1. Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA
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  • Julin Yang,

    1. Ningbo College of Health Sciences, Ningbo, China
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  • Yan-Yan Zhang,

    1. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
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  • Rong-Rong He,

    1. Pharmacy College, Jinan University, Guangzhou, China
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  • Xu Zhu,

    1. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
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  • Zhen-Wen Yu,

    1. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
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  • Xiao-Yu Sun,

    1. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
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  • Mo Hong,

    1. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
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  • Lu Yang

    1. Joint Center for Translational Medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences and The first Affiliated Hospital of Liaoning Medical University, Dalian, China
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Correspondence to: Bin Guo, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.

E-mail: Guobin@163.com

Abstract

The detailed mechanisms on licorice–drug interaction remain to be unclear. The aim of the present study is to investigate the inhibition of important UGT isoforms by two important ingredients of licorice, liquiritin, and liquiritigenin. The results showed that liquiritigenin exhibited stronger inhibition towards all the tested UGT isoforms than liquiritin. Data fitting using Dixon and Lineweaver–Burk plots demonstrated the competitive inhibition of liquiritigenin towards UGT1A1 and UGT1A9-mediated 4-MU glucuronidation reaction. The inhibition kinetic parameters (Ki) were calculated to be 9.1 and 3.2 μM for UGT1A1 and UGT1A9, respectively. Substrate-dependent inhibition behaviour was also observed for UGT1A1 in the present study. All these results will be helpful for understanding the deep mechanism of licorice–drug interaction. However, when translating these in vitro parameters into in vivo situations, more complex factors should be considered, such as substrate-dependent inhibition of UGT isoforms, the contribution of UGT1A1 and UGT1A9 towards the metabolism of drugs, and many factors affecting the abundance of ingredients in the licorice. Copyright © 2012 John Wiley & Sons, Ltd.

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