title: Probe substrate and enzyme source-dependent inhibition of UDP-glucuronosyltransferase (UGT) 1A9 by wogonin.
abstract: BACKGROUND
  Drug-metabolizing enzymes (DMEs) inhibition based drug-drug interaction and herb-drug interaction severely challenge the R&D process of drugs or herbal ingredients.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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 situation.
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, P. R. China.
authors.forename: Gao
authors.initials: G
authors.lastname: Chengcheng
authors.forename: Xie
authors.initials: X
authors.lastname: Rui
authors.forename: Ma
authors.initials: M
authors.lastname: Tianheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Wei
authors.forename: Pang
authors.initials: P
authors.lastname: Liqun
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044950:Flavanones / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D006923:Hymecromone / Q000037:antagonists & inhibitors; D007202:Indicators and Reagents; D008862:Microsomes, Liver / Q000187:drug effects; D000090264:UDP-Glucuronosyltransferase 1A9
chemical_list: D004791:Enzyme Inhibitors; D044950:Flavanones; D007202:Indicators and Reagents; C000715591:UGT1A9 protein, human; D006923:Hymecromone; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; C085514:wogonin
keywords: UDP-glucuronosyltransferases (UGTs); drug-drug interaction (DDI); wogonin