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Published:
Sep 10, 2015DOI:
10.4314/ahs.v15i3.40Keywords:
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Main Article Content
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.
Aims: 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.
Conslusion: 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.
Keywords: UDP-glucuronosyltransferases(UGTs), drug-drug interaction, oleanolic acid, betulinic acid
