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

• DOI: 10.3892/etm.2021.10274
• Publication Date: 2021-06-06T19:39:50Z
• Authors: Rui Zhang; Ye Wei; Tingyu Yang; Xixi Huang; Jinping Zhou; Chunxiao Yang; Jiani Zhou; Yani Liu; Shaojun Shi
• Keywords: 0301 basic medicine; 03 medical and health sciences; Articles; 3. Good health

Quercetin is a flavonoid that widely present in plant‑derived food. Quercetin‑3‑O‑β‑D‑glucoside (Q3GA) predominant metabolite of quercetin animal and human plasma. The inhibitory effects the UDP‑glucuronosyl transferases (UGTs) caused by herbal components may be key factor for clinical assessment herb‑drug interactions (HDIs). study aimed to investigate profile Q3GA on recombinant UGT1A isoforms <em>in vitro</em>. metabolism nonspecific substrate 4‑methylumbelliferone (4‑MU) was assessed liquid chromatography‑tandem mass spectrometry. Preliminary screening experiments indicated exhibited stronger UGT1A1, UGT1A3, UGT1A6 UGT1A9 enzymes than Q3GA. Kinetic were performed characterize type inhibition towards these UGT isoforms. exerted non‑competitive UGT1A1 UGT1A6, with half maximal concentration (IC₅₀) values 7.47 7.07 <em>µ</em>M kinetic parameter (Ki) 2.18 28.87 <em>µ</em>M, respectively. also competitive UGT1A3 UGT1A9, IC₅₀ 10.58 2.81 Ki 1.60 0.51 However, displayed weak 45.21, 106.5 51.37 In study, moderate inhibitor strong UGT1A9. results suggested potential HDIs occur following co‑administration drugs are mainly metabolized enzymes.