title: In vitro evidence for bakuchiol's influence towards drug metabolism through inhibition of UDP-glucuronosyltransferase (UGT) 2B7.
abstract: BACKGROUND
  Inhibition of drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reason for clinical drug-drug interaction.
  
  
  OBJECTIVE
  The aim of the present study is to evaluate the inhibition of bakuchiol towards UDP-glucuronosyltransferase (UGT) 2B isoforms.
  
  
  METHODS
  In vitro recombinant UGT2B-catalyzed 4-methylumbelliferone glucuronidation was used as the probe reaction. Dixon plot and Lineweaver-Burk plot were employed to determine the inhibition kinetic type, and nonlinear regression of data was utilized to calculate the inhibition kinetic parameter (Ki). In vitro-in vivo extrapolation (IVIVE) was carried out to predict in vivo inhibition magnitude.
  
  
  RESULTS
  Among the tested UGT2B isoforms, UGT2B7 was inhibited by the strongest intensity. The noncompetitive inhibition was demonstrated by the results obtained from Dixon plot and Lineweaver-Burk plot. The Ki value was calculated to be 10.7 µM. In combination with the reported concentration after an intravenous administration of bakuchiol (15 mg/kg) in rats, the high risk of in vivo inhibition of bakuchiol towards UGT2B7-catalyzed metabolism of drugs was indicated.
  
  
  CONCLUSIONS
  All these results provide an important information for the risk evaluation of the clinical utilization of bakuchiol.
authors.affiliation: Department of Otorhinolaryngology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Otorhinolaryngology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, P. R. China.
authors.forename: Peizhong
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, P. R. China.
authors.forename: Junying
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, P. R. China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Gu
authors.affiliation: Pharmaceutical Preparation Section, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, P. R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D000099148:UGT1A1 Enzyme
chemical_list: D004791:Enzyme Inhibitors; D014453:Glucuronosyltransferase; D007527:Isoenzymes; D010636:Phenols; D000099148:UGT1A1 Enzyme; C012765:bakuchiol
keywords: bakuchiol; drug-drug interaction; drug-metabolizing enzymes