title: Comparison of the inhibition capability of oleanolic acid and betulinic acid towards drug-metabolizing enzymes.
abstract: BACKGROUND
  Human UDP-glucuronosyltransferases (UGTs) are important membrane proteins located in endoplasmic reticulum, and play important roles in metabolism of a variety of endogenous and exogenous compounds.
  
  
  OBJECTIVE
  To determine the influence of subtle difference in the structure of oleanolic acid and betulinic acid towards the inhibition towards the activity of UGT isoforms.
  
  
  METHODS
  In vitro glucuronidation of 4-methylumbelliferone (4-MU) reaction was employed as the probe reaction to determine the inhibition of these two compounds towards UGTs' activity.
  
  
  RESULTS
  The inhibition of capability of oleanolic acid towards UGT1A6 and UGT1A8 were higher than betulinic acid. However, no significant difference was observed for the inhibition of oleanolic acid and betulinic acid towards UGT1A7. Furthermore, concentration-dependent behaviour was determined for the inhibition of oleanolic acid and betulinic acid towards UGT1A6 and UGT1A8. At various concentrations of oleanolic acid and betulinic acid, the inhibition of oleanolic acid towards UGT1A6 and UGT1A8 was higher than betulinic acid.
  
  
  CONCLUSIONS
  Given that UGT1A6 and UGT1A8 play key role in the the inhibition of oleanolic acid towards UGT1A6 and UGT1A8 will induce drug-drug interaction and the risk of diseases.
authors.affiliation: Department of Infectious Diseases, Xiangya Hospital of Central South University, Changsha, Hu'nan 410008, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Infectious Diseases, Xiangya Hospital of Central South University, Changsha, Hu'nan 410008, China.
authors.forename: Meng-Hou
authors.initials: MH
authors.lastname: Lu
mesh_terms: D004347:Drug Interactions; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D006923:Hymecromone / Q000378:metabolism*; D009828:Oleanolic Acid / Q000494:pharmacology*; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D006923:Hymecromone; D009828:Oleanolic Acid; D014453:Glucuronosyltransferase; D000094062:Betulinic Acid
keywords: UDP-glucuronosyltransferases(UGTs); betulinic acid; drug-drug interaction; oleanolic acid