Glycyrrhetinic Acid Exhibits Strong Inhibitory Effects Towards UDP‐Glucuronosyltransferase (UGT) 1A3 and 2B7

The aim of the present study is to evaluate the inhibitory effects of liver UDP‐glucuronosyltransferases (UGTs) by glycyrrhizic acid and glycyrrhetinic acid, which are the bioactive ingredients isolated from licorice. The results showed that glycyrrhetinic acid exhibited stronger inhibition towards all the tested UGT isoforms, indicating that the deglycosylation process played an important role in the inhibitory potential towards UGT isoforms. Furthermore, the inhibition kinetic type and parameters were determined for the inhibition of glycyrrhetinic acid towards UGT1A3 and UGT2B7. Data fitting using Dixon and Lineweaver‐Burk plots demonstrated that the inhibition of UGT1A3 and UGT2B7 by glycyrrhetinic acid was best fit to competitive and noncompetitive type, respectively. The second plot using the slopes from Lineweaver‐Burk plots versus glycyrrhetinic acid concentrations was employed to calculate the inhibition kinetic parameters (K_i), and the values were calculated to be 0.2 and 1.7 μM for UGT1A3 and UGT2B7, respectively. All these results remind us the possibility of UGT inhibition‐based herb–drug interaction. However, the explanation of these in vitro parameters should be paid more caution due to complicated factors, including the probe substrate‐dependent UGT inhibition behaviour, environmental factors affecting the abundance of herbs' ingredients, and individual difference of pharmacokinetic factors. Copyright © 2012 John Wiley & Sons, Ltd.