Issue 72, 2018

Glucuronidation of [6]-shogaol, [8]-shogaol and [10]-shogaol by human tissues and expressed UGT enzymes: identification of UGT2B7 as the major contributor

Abstract

Shogaols, mainly [6]-shogaol (6S), [8]-shogaol (8S) and [10]-shogaol (10S), the predominant and characteristic pungent phytochemicals in ginger, are responsible for most of its beneficial effects. However, poor oral bioavailability owing to extensive glucuronidation limits their application. The present study aimed to characterize the glucuronidation pathways of 6S, 8S and 10S by using pooled human liver microsomes (HLM), human intestine microsomes (HIM) and recombinant human UDP-glucosyltransferases (UGTs). The rates of glucuronidation were determined by incubating shogaols with uridine diphosphate glucuronic acid-supplemented microsomes. Kinetic parameters were derived by appropriate model fitting. Reaction phenotyping assays, activity correlation analyses and relative activity factors were performed to identify the main UGT isoforms. As a result, one mono-4′-O-glucuronide was detected after incubating each shogaol with HLM and HIM. Enzymes kinetic analysis demonstrated that glucuronidation of shogaols consistently displayed the substrate inhibition profile, and the liver showed higher metabolic activity for shogaols (CLint = 1.37–2.87 mL min−1 mg−1) than the intestine (CLint = 0.67–0.85 mL min−1 mg−1). Besides, reaction phenotyping assays revealed that UGT2B7 displayed the highest catalytic ability (CLint = 0.47–1.17 mL min−1 mg−1) among all tested UGTs. In addition, glucuronidation of shogaols was strongly correlated with AZT glucuronidation (r = 0.886, 0.803 and 0.871 for glucuronidation of 6S, 8S and 10S, respectively; p < 0.01) in a bank of individual HLMs (n = 9). Furthermore, UGT2B7 contributed to 40.8%, 34.2% and 36.0% for the glucuronidation of 6S, 8S and 10S in HLM, respectively. Taken altogether, shogaols were efficiently metabolized through the glucuronidation pathway, and UGT2B7 was the main contributor to their glucuronidation.

Graphical abstract: Glucuronidation of [6]-shogaol, [8]-shogaol and [10]-shogaol by human tissues and expressed UGT enzymes: identification of UGT2B7 as the major contributor

Supplementary files

Article information

Article type
Paper
Submitted
12 Oct 2018
Accepted
26 Nov 2018
First published
12 Dec 2018
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2018,8, 41368-41375

Glucuronidation of [6]-shogaol, [8]-shogaol and [10]-shogaol by human tissues and expressed UGT enzymes: identification of UGT2B7 as the major contributor

L. He, J. Xu, Q. Wang, Y. Zhang, Z. Qin, Y. Yu, Z. Qian, Z. Yao and X. Yao, RSC Adv., 2018, 8, 41368 DOI: 10.1039/C8RA08466A

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements