Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, NC, USA.
Mol Nutr Food Res. 2017 Sep;61(9). doi: 10.1002/mnfr.201700023. Epub 2017 Jul 3.
-shogaol (6S) from ginger has been reported to have diverse bioactivities and can be widely metabolized in animals and humans; however, the impact of glucuronidation on its bioactivity is still largely unknown. This study investigates the glucuronidation of 6S and its effect on cell cytotoxicity and Nrf2-inducing activities of 6S.
The glucuronidated metabolite of 6S, 4-O-monoglucuronide 6S (6S-G), was synthesized and characterized for the first time. Glucuronidation of 6S in humans was studied using microsomes of the liver and intestine and recombinant UDP-glucuronosyltransferase (UGTs). The kinetics of 6S glucuronidation by human liver and intestinal microsomes followed the substrate inhibition kinetics model. The intrinsic glucuronidation clearance (CL ) of 6S in human liver microsomes was higher than that in human intestine microsomes. Among the recombinant UGTs examined, UGT1A1, 1A3, 1A6, 1A8, 1A10, 2B7, 2B15, and 2B17 exhibited glucuronidation activity toward 6S, with UGT2B7 being the most potent one. Compared with 6S, the glucuronidation of 6S largely eliminated its cell cytotoxicity against human colon cancer cell lines HT-116 and HT-29, and its Nrf2-inducing activity.
The findings from current study provide foundations for understanding the role of glucuronidation in biotransformation and biological activities of 6S.
-shogaol（6S）来自生姜，具有多种生物活性，可在动物和人体中广泛代谢；然而，其生物活性的糖基化作用在很大程度上仍不清楚。本研究调查了 6S 的糖基化及其对细胞细胞毒性和 6S 的 Nrf2 诱导活性的影响。
首次合成并表征了 6S 的糖基化代谢产物 4-O-单葡萄糖苷 6S（6S-G）。使用肝和肠微粒体和重组 UDP-葡糖醛酸基转移酶（UGTs）研究了 6S 在人体内的糖基化。6S 的人肝和肠微粒体糖基化的动力学遵循底物抑制动力学模型。人肝微粒体中 6S 的内在糖基化清除率（CL）高于人肠微粒体。在所检查的重组 UGT 中，UGT1A1、1A3、1A6、1A8、1A10、2B7、2B15 和 2B17 对 6S 具有糖基化活性，其中 UGT2B7 是最有效的一种。与 6S 相比，6S 的糖基化大大消除了其对人结肠癌细胞系 HT-116 和 HT-29 的细胞毒性及其 Nrf2 诱导活性。
本研究的结果为理解糖基化在 6S 的生物转化和生物学活性中的作用提供了基础。
