Ruefer Corinna E, Gerhäuser Clarissa, Frank Norbert, Becker Hans, Kulling Sabine E
Institute of Nutritional Physiology, Federal Research Centre for Nutrition and Food, Karlsruhe, Germany.
Mol Nutr Food Res. 2005 Sep;49(9):851-6. doi: 10.1002/mnfr.200500057.
Xanthohumol (XN) is the principal prenylated flavonoid of the hop plant and has recently gained considerable interest due to its potential cancer-chemopreventive effects. However, the metabolism of XN has not yet been investigated in detail. Therefore, we studied the in vitro phase II metabolism of XN using nine human recombinant UDP-glucuronosyltransferases (UGT) and five sulfotransferases (SULT). The identification of the metabolites formed was elucidated using HPLC with diode array detection as well as HPLC/API-ES MS. XN was efficiently glucuronidated by UGT 1 A 8, 1 A 9, and 1 A 10; further important UGTs were UGT 1 A 1, 1 A 7, and 2 B 7. With respect to the sulfation reaction, SULT 1 A 1*2, 1 A 2, and 1 E 1 were the most active SULT forms. UGT 1 A 3, 1 A 4, and 1 A 6 as well as SULT 1 A 3 and 2 A 1 were of minor importance for the conjugation of XN. Three mono-glucuronides as well as three mono-sulfates were identified. Considering the tissue distribution of the tested UGT and SULT enzyme forms, these findings suggest a prominent role for the glucuronidation and sulfation of XN in the liver as well as in the gastrointestinal tract.
黄腐酚（XN）是啤酒花植物中主要的异戊烯基黄酮，由于其潜在的癌症化学预防作用，近年来备受关注。然而，XN的代谢尚未得到详细研究。因此，我们使用九种人重组尿苷二磷酸葡萄糖醛酸基转移酶（UGT）和五种磺基转移酶（SULT）研究了XN的体外Ⅱ相代谢。通过带有二极管阵列检测的高效液相色谱法以及高效液相色谱/大气压光电离质谱法阐明了所形成代谢物的鉴定。XN被UGT 1 A 8、1 A 9和1 A 10有效地葡萄糖醛酸化；其他重要的UGT是UGT 1 A 1、1 A 7和2 B 7。关于硫酸化反应，SULT 1 A 1*2、1 A 2和1 E 1是最具活性的SULT形式。UGT 1 A 3、1 A 4和1 A 6以及SULT 1 A 3和2 A 1对XN的结合作用较小。鉴定出了三种单葡萄糖醛酸苷以及三种单硫酸盐。考虑到所测试的UGT和SULT酶形式的组织分布，这些发现表明XN的葡萄糖醛酸化和硫酸化在肝脏以及胃肠道中起重要作用。
