Deglycosylation of liquiritin strongly enhances its inhibitory potential towards UDP-glucuronosyltransferase (UGT) isoforms.
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.
The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China. Guobin@163.com
Bin
B
Guo
Xu-Ran
XR
Fan
Zhong-Ze
ZZ
Fang
Yun-Feng
YF
Cao
Cui-Min
CM
Hu
Julin
J
Yang
Yan-Yan
YY
Zhang
Rong-Rong
RR
He
Xu
X
Zhu
Zhen-Wen
ZW
Yu
Xiao-Yu
XY
Sun
Mo
M
Hong
Lu
L
Yang
D044950:Flavanones / Q000737:chemistry*; D018565:Food-Drug Interactions; D005960:Glucosides / Q000737:chemistry*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006035:Glycyrrhiza / Q000737:chemistry; D006801:Humans; D006923:Hymecromone / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D000090264:UDP-Glucuronosyltransferase 1A9; D000099148:UGT1A1 Enzyme
D044950:Flavanones; D005960:Glucosides; D014453:Glucuronosyltransferase; D006923:Hymecromone; D007527:Isoenzymes; D000090264:UDP-Glucuronosyltransferase 1A9; D000099148:UGT1A1 Enzyme; C000715591:UGT1A9 protein, human; C512196:liquiritin; C083152:liquiritigenin