Biotransformation of baicalin to baicalein significantly strengthens the inhibition potential towards UDP-glucuronosyltransferases (UGTs) isoforms.

The aim of the present study was to investigate the influence of biotransformation of baicalin into baicalein towards the inhibition potential towards one of the most important drug-metabolizing enzymes (DMEs) UDP-glucuronosyltransferases (UGTs). in vitro incubation method using recombinant UGTs-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was used to evaluate the inhibition towards important UGT isoforms in the liver, including UGT1A1, 1A3, 1A6, 1A9, and 2B7. At the same concentration (100 microM), baicalein showed stronger inhibition potential than baicalin towards all the tested UGT isoforms. Data fitting using Dixon plot and Lineweaver-Burk plot was carried out to determine the inhibition type, and the second plot with the slopes from Lineweaver-Burk plot towards baicalein's concentrations was used to calculate the inhibition kinetic parameters (K(i)). Competitive inhibition type was observed for UGT1A1, 1A6, 1A9 and 2B7, and noncompetitive inhibition was detected for UGT1A3. The inhibition kinetic parameters (K(i)) were calculated to be 1.2, 5.1, 15.3, 26.3, and 48.9 microM for UGT1A1, 1A3, 1A6, 1A9, and 2B7, respectively. All these information reminds us of the necessary monitoring when oral administration of baicalin or baicalin-containing herbs.