Drug-metabolizing enzymes (DMEs) inhibition based drug-drug interaction and herb-drug interaction severely challenge the R&D process of drugs or herbal ingredients.
To evaluate the inhibition potential of wogonin (an important flavonoid isolated from the root of Scutellaria baicalensis
) towards one of the most important phase II DMEs, UDP-glucuronosyltransferase (UGT) 1A9.
Both recombinant UGT1A9-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and human liver microsomes (HLMs)-catalyzed propofol glucuronidation reaction were used as two different probe reactions.
Wogonin noncompetitively inhibited recombinant UGT1A9-catalyzed 4-MU glucuronidation, and exerted
competitive inhibition towards HLMs-catalyzed propofol glucuronidation. The inhibition kinetic parameters (Ki) were calculated to be 3.2 μM and 52.0μM, respectively.
Necessary monitoring was needed when wogonin was co-administered with the clinical drugs mainly undergoing UGT1A9-mediated glucuronidation elimination. Additionally, probe reactions-dependent inhibition of wogonin towards the activity of UGT1A9 should be paid attention when translating these in vitro
data into in vivo