Hanioka Nobumitsu, Isobe Takashi, Tanaka-Kagawa Toshiko, Ohkawara Susumu
Department of Health Pharmacy, Yokohama University of Pharmacy, Yokohama, Japan.
Xenobiotica. 2020 Aug;50(8):906-912. doi: 10.1080/00498254.2020.1725180. Epub 2020 Feb 12.
Wogonin, one of the flavonoids isolated from , 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. values (-intercept) based on versus /[] 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. values were rats > monkeys > mice > dogs > humans. The tissue dependence of 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.
汉黄芩素是从[具体来源未给出]中分离出的黄酮类化合物之一,具有一些有益的生物活性,包括抗炎和抗癌作用,在人体内可被尿苷二磷酸葡萄糖醛酸基转移酶(UGT)代谢为葡萄糖醛酸苷。在本研究中,采用动力学分析方法检测了人、猴、犬、大鼠和小鼠肝脏及肠道微粒体中汉黄芩素的葡萄糖醛酸化情况。在所检测的所有物种中,肝脏微粒体对汉黄芩素葡萄糖醛酸化的动力学均符合双相模型。基于对[具体物质]与/[]作图得到的米氏常数(-截距)值为大鼠>人≈猴>小鼠>犬。肠道微粒体的动力学对人、猴、大鼠和小鼠符合米氏方程模型,对犬符合底物抑制模型。米氏常数的值为大鼠>猴>小鼠>犬>人。对于人、犬和大鼠,米氏常数的值在组织依赖性上为肝脏微粒体>肠道微粒体,对于猴和小鼠,肝脏微粒体≈肠道微粒体。这些结果表明,UGT酶对汉黄芩素在肝脏和肠道中的代谢能力在人、猴、犬、大鼠和小鼠之间存在显著差异,提示物种差异与汉黄芩素的生物学效应密切相关。