Inhibitory effects of quercetin and its major metabolite quercetin-3-O-β-D-glucoside on human UDP-glucuronosyltransferase 1A isoforms by liquid chromatography-tandem mass spectrometry.
Inhibitory effects of quercetin and its major metabolite quercetin-3-O-β-D-glucoside on human UDP-glucuronosyltransferase 1A isoforms by liquid chromatography-tandem mass spectrometry.
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液相色谱-串联质谱法测定槲皮素及其主要代谢物槲皮素-3-O-D-葡萄糖苷对人UDP-葡萄糖醛酸基转移酶1A亚型的抑制作用
DOI：
10.3892/etm.2021.10274
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发表时间：
2021-08
影响因子：
2.7
通讯作者：
Shi S
中科院分区：
文献类型：
--
作者：
Zhang R;Wei Y;Yang T;Huang X;Zhou J;Yang C;Zhou J;Liu Y;Shi S
槲皮素是一种黄酮类化合物，广泛存在于植物源性食品中。槲皮素-3-O-β-D-葡萄糖苷（Q3 GA）是槲皮素在动物和人血浆中的主要代谢产物。中药成分对尿苷二磷酸葡萄糖醛酸转移酶（UGT）的抑制作用可能是临床评价中药相互作用（HDI）的关键因素。本研究旨在研究槲皮素和Q3 GA对重组UGT 1A亚型的体外抑制作用。通过液相色谱-串联质谱法评估UGT 1A亚型对非特异性底物4-甲基伞形酮（4-MU）的代谢。初步筛选实验表明，槲皮素对UGT 1A 1、UGT 1A 3、UGT 1A 6和UGT 1A 9酶的抑制作用强于Q3 GA。进行动力学实验以表征槲皮素和Q3 GA对这些UGT亚型引起的抑制类型。槲皮素对UGT 1A 1和UGT 1A 6具有非竞争性抑制作用，半数最大抑制浓度（IC 50）值分别为7.47和7.07 µM，抑制动力学参数（Ki）值分别为2.18和28.87 µM。槲皮素还对UGT 1A 3和UGT 1A 9表现出竞争性抑制作用，IC 50值分别为10.58和2.81 µM，Ki值分别为1.60和0.51 µM。然而，Q3 GA对UGT 1A 1、UGT 1A 3和UGT 1A 6酶显示出较弱的抑制作用，IC 50值分别为45.21、106.5和51.37 µM。在本研究中，槲皮素是UGT 1A 1和UGT 1A 3的中度抑制剂，UGT 1A 6的弱抑制剂，UGT 1A 9的强抑制剂。本研究的结果表明，槲皮素与主要由UGT 1A 1、UGT 1A 3和UGT 1A 9酶代谢的药物联合给药后可能发生潜在的HDI。
Quercetin is a flavonoid that is widely present in plant-derived food. Quercetin-3-O-β-D-glucoside (Q3GA) is a predominant metabolite of quercetin in animal and human plasma. The inhibitory effects of the UDP-glucuronosyl transferases (UGTs) caused by herbal components may be a key factor for the clinical assessment of herb-drug interactions (HDIs). The present study aimed to investigate the inhibitory profile of quercetin and Q3GA on recombinant UGT1A isoforms in vitro. The metabolism of the nonspecific substrate 4-methylumbelliferone (4-MU) by the UGT1A isoforms was assessed by liquid chromatography-tandem mass spectrometry. Preliminary screening experiments indicated that quercetin exhibited stronger inhibitory effects on UGT1A1, UGT1A3, UGT1A6 and UGT1A9 enzymes than Q3GA. Kinetic experiments were performed to characterize the type of inhibition caused by quercetin and Q3GA towards these UGT isoforms. Quercetin exerted non-competitive inhibition on UGT1A1 and UGT1A6, with half maximal inhibitory concentration (IC50) values of 7.47 and 7.07 µM and inhibition kinetic parameter (Ki) values of 2.18 and 28.87 µM, respectively. Quercetin also exhibited competitive inhibition on UGT1A3 and UGT1A9, with IC50 values of 10.58 and 2.81 µM and Ki values of 1.60 and 0.51 µM, respectively. However, Q3GA displayed weak inhibition on UGT1A1, UGT1A3 and UGT1A6 enzymes with IC50 values of 45.21, 106.5 and 51.37 µM, respectively. In the present study, quercetin was a moderate inhibitor of UGT1A1 and UGT1A3, a weak inhibitor of UGT1A6, and a strong inhibitor on UGT1A9. The results of the present study suggested potential HDIs that may occur following quercetin co-administration with drugs that are mainly metabolized by UGT1A1, UGT1A3 and UGT1A9 enzymes.
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影响因子：
--
作者：
Costa LG;Garrick JM;Roquè PJ;Pellacani C
通讯作者：
Pellacani C
关于双酚 A 风险的新见解：抑制 UDP-葡萄糖醛酸基转移酶 (UGT)。
影响因子：
8.8
作者：
Jiang, Hua-Mao;Fang, Zhong-Ze;Liu, Ren-Jie
通讯作者：
Liu, Ren-Jie
槲皮素诱导的药物代谢酶和转运蛋白表达变化对环孢素在大鼠体内药代动力学的影响
影响因子：
3.4
作者：
Liu Y;Luo X;Yang C;Yang T;Zhou J;Shi S
通讯作者：
Shi S
DOI：
10.1016/j.bbrc.2013.01.056
发表时间：
2013-02-22
影响因子：
3.1
作者：
Byun, Eui-Baek;Yang, Mi-So;Byun, Eui-Hong
通讯作者：
Byun, Eui-Hong
影响因子：
1.6
作者：
Huang, T.;Fang, Z. Z.;Yang, L.
通讯作者：
Yang, L.