Wogonin glucuronidation in liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice
Wogonin glucuronidation in liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice
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DOI：
10.1080/00498254.2020.1725180
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发表时间：
2020-02-11
期刊：
影响因子：
1.8
通讯作者：
Ohkawara, Susumu
中科院分区：
文献类型：
--
作者：
Hanioka, Nobumitsu;Isobe, Takashi;Ohkawara, Susumu
汉黄素是从黄芩中分离得到的一种黄酮类化合物，具有抗炎、抗癌等多种生物活性，在人体内被UDP-葡萄糖醛酸基转移酶(UGT)代谢为葡萄糖醛酸苷。在本研究中，用动力学分析的方法检测了汉黄素在人、猴、狗、大鼠和小鼠的肝脏和肠道微粒体中的葡萄糖醛酸化作用。在所研究的所有物种中，汉黄素葡醛酸化动力学符合双相模型。基于v和V/[S]曲线图的斜坡值(x-截距)是大鼠和人，与猴子和小鼠和狗相似。人、猴、大鼠和小鼠的肠道微生物体动力学符合Michaelis-Menten模型，狗符合底物抑制模型。克林特值为大鼠、猴子、小鼠、狗和人。对于人、狗和大鼠来说，克林特值的组织依赖性是肝微体和肠道微体，而对于猴子和小鼠来说，肝微体近似于肠道微体。这些结果表明，人、猴、狗、大鼠和小鼠肝脏和肠道中UGT酶对汉黄素的代谢能力明显不同，提示物种差异与汉黄素的生物学效应密切相关。
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. CLint values (x-intercept) based on v versus V/[S] plots were rats > humans approximate to 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. CLint values were rats > monkeys > mice > dogs > humans. The tissue dependence of CLint values was liver microsomes > intestinal microsomes for humans, dogs, and rats, and liver microsomes approximate to 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.