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

Author:

Bin Guo  Xu-Ran Fan  Zhong-Ze Fang  Yun-Feng Cao  Cui-Min Hu  Julin Yang  Yan-Yan Zhang  Rong-Rong He  Xu Zhu  Zhen-Wen Yu  Xiao-Yu Sun  Mo Hong and Lu Yang  

Journal:

Phytotherapy Research

Issue Date:

2013

Abstract(summary):

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

Page:

1232-1236