Wogonin glucuronidation in liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice

Wogonin, one of the Flavonoids isolated from Scutellaria baicalensis, exhibits some beneficial bioactivities, including anti-inflammatory and Anticancer effects, and is metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in humans. In the present study, wogonin glucuronidation was examined in the liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice using a kinetic analysis.The kinetics of wogonin glucuronidation by liver microsomes followed the biphasic model in all species examined. CL_int values (x-intercept) based on v versus V/[S] plots were rats > humans ≈ monkeys > mice > dogs. The kinetics of intestinal microsomes fit the Michaelis-Menten model for humans, monkeys, rats, and mice and the substrate inhibition model for dogs. CL_int values were rats > monkeys > mice > dogs > humans. The tissue dependence of CL_int values was liver microsomes > intestinal microsomes for humans, dogs, and rats, and liver microsomes ≈ intestinal microsomes for monkeys and mice.These results demonstrated that the metabolic abilities of UGT enzymes toward wogonin in the liver and intestines markedly differ among humans, monkeys, dogs, rats, and mice, and suggest that species differences are closely associated with the biological effects of wogonin.