Department of Health Pharmacy, Yokohama University of Pharmacy.
Faculty of Pharmacy, Meijo University.
Biol Pharm Bull. 2022;45(8):1116-1123. doi: 10.1248/bpb.b22-00160.
Flavones, which are distributed in a variety of plants and foods in nature, possess significant biological activities, including antitumor and anti-inflammatory effects, and are metabolized into glucuronides by uridine 5'-diphosphate (UDP)-glucuronosyltransferase (UGT) enzymes in humans. In this study, apigenin, acacetin, and genkwanin, flavones having hydroxyl groups at C5, C7, and/or C4'positions were focused on, and the regioselective glucuronidation in human liver and intestinal microsomes was examined. Two glucuronides (namely, AP-7G and AP-4'G for apigenin, AC-5G and AC-7G for acacetin, and GE-5G and GE-4'G for genkwanin) were formed from each flavone by liver and intestinal microsomes, except for only GE-4'G formation from genkwanin by intestinal microsomes. The order of total glucuronidation activities was liver microsomes > intestinal microsomes for apigenin and acacetin, and liver microsomes < intestinal microsomes for genkwanin. The order of CL values (x-intercept) based on v versus V/[S] plots for apigenin glucuronidation was AP-7G > AP-4'G in liver microsomes and AP-7G < AP-4'G in intestinal microsomes. The order of CL values was AC-5G < AC-7G for acacetin and GE-5G < GE-4'G genkwanin glucuronidation in both liver and intestinal microsomes. This suggests that the abilities and roles of UGT enzymes in the glucuronidation of apigenin, acacetin, and genkwanin in humans differ depending on the chemical structure of flavones.
黄酮类化合物广泛分布于自然界中的各种植物和食物中，具有显著的生物活性，包括抗肿瘤和抗炎作用，并在人体内被尿苷 5′-二磷酸（UDP）-葡萄糖醛酸基转移酶（UGT）酶代谢为葡萄糖醛酸苷。在这项研究中，专注于具有 C5、C7 和/或 C4'位羟基的黄酮类化合物，如芹菜素、木犀草素和金雀异黄素，研究了人肝和肠微粒体中的区域选择性葡萄糖醛酸化。除了金雀异黄素仅在肠微粒体中形成 GE-4'G 外，每种黄酮类化合物均由肝和肠微粒体形成两种葡萄糖醛酸苷（即芹菜素的 AP-7G 和 AP-4'G、木犀草素的 AC-5G 和 AC-7G 以及金雀异黄素的 GE-5G 和 GE-4'G）。对于芹菜素和木犀草素，总葡萄糖醛酸化活性的顺序为肝微粒体>肠微粒体，而对于金雀异黄素则为肝微粒体<肠微粒体。基于 v 对 V/[S]图的 AP-7G 葡萄糖醛酸化的 CL 值（x 截距）的顺序为肝微粒体中 AP-7G>AP-4'G，而肠微粒体中 AP-7G<AP-4'G。对于乙酰化木犀草素和金雀异黄素葡萄糖醛酸化，CL 值的顺序为 AC-5G<AC-7G，而 GE-5G<GE-4'G。这表明 UGT 酶在人体内对芹菜素、木犀草素和金雀异黄素葡萄糖醛酸化的能力和作用因黄酮类化合物的化学结构而异。
