BACKGROUND: The glucuronidation process has been regarded as the key elimination process for toxic bile acids. UDP-glucuronosyltransferase (UGT) 1A3 is one important metabolizing enzyme involved in this process. OBJECTIVE: To evaluate the inhibition of UGT1A3 by scutellarein which is an important herbal ingredient using in vitro method, trying to indicate the possibility of toxicity due to the accumulation of toxic bile acids. METHODS: Due to the difficulty to gain the standards of biles acids' glucuronides, the recombinant UGT1A3-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction was employed to profile the activity of UGT1A3. RESULTS: The results showed that scutellarein inhibited UGT1A3 in a concentration-dependent behaviour. Competitive inhibition was demonstrated using both Dixon plot and Lineweaver-Burk plot, and the inhibition kinetic parameter (Ki) was calculated to be 5.8uM. CONCLUSION: All these data reminded the necessary monitoring of the levels of bile acids in plasma when utilizing scutellarein and the herbs containing this compound.
BACKGROUND: The glucuronidation process has been regarded as the key elimination process for toxic bile acids. UDP-glucuronosyltransferase (UGT) 1A3 is one important metabolizing enzyme involved in this process. OBJECTIVE: To evaluate the inhibition of UGT1A3 by scutellarein which is an important herbal ingredient using in vitro method, trying to indicate the possibility of toxicity due to the accumulation of toxic bile acids. METHODS: Due to the difficulty to gain the standards of biles acids' glucuronides, the recombinant UGT1A3-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction was employed to profile the activity of UGT1A3. RESULTS: The results showed that scutellarein inhibited UGT1A3 in a concentration-dependent behaviour. Competitive inhibition was demonstrated using both Dixon plot and Lineweaver-Burk plot, and the inhibition kinetic parameter (Ki) was calculated to be 5.8uM. CONCLUSION: All these data reminded the necessary monitoring of the levels of bile acids in plasma when utilizing scutellarein and the herbs containing this compound.
Entities:
Keywords:
bile acids metabolism; in vitro methods; scutellarein
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