Characterization of thiol-conjugated metabolites of ginger components shogaols in mouse and human urine and modulation of the glutathione levels in cancer cells by -shogaol
Article first published online: 16 JAN 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 57, Issue 3, pages 447–458, March 2013
How to Cite
Chen, H., Soroka, D. N., Hu, Y., Chen, X. and Sang, S. (2013), Characterization of thiol-conjugated metabolites of ginger components shogaols in mouse and human urine and modulation of the glutathione levels in cancer cells by -shogaol. Mol. Nutr. Food Res., 57: 447–458. doi: 10.1002/mnfr.201200679
- Issue published online: 12 MAR 2013
- Article first published online: 16 JAN 2013
- Manuscript Accepted: 21 NOV 2012
- Manuscript Revised: 7 NOV 2012
- Manuscript Received: 14 OCT 2012
- investigation was provided. Grant Number: CA138277
- National Cancer Institute. Grant Number: CA138277S1
- National Cancer Institute and Office of Dietary Supplement of National Institutes of Health
- Human urine;
- Thiol-conjugated metabolites
Shogaols, a series of major constituents in dried ginger with the most abundant being -, -, and -shogaols, show much higher anticancer potencies than gingerols. Previously, we reported the mercapturic acid pathway as a major metabolic route for -shogaol in mice. However, it is still unclear how the side chain length affects the metabolism of shogaols and how shogaols are metabolized in humans.
Methods and results
We first investigate the metabolism of -shogaol in mouse urine, and then investigate the biotransformation of shogaols in human urine. Our results show that eight major thiol-conjugated metabolites of -shogaol were detected in mouse urine, while six major thiol-conjugated metabolites of -shogaol, two thiol-conjugated metabolites of -shogaol, and two thiol-conjugated metabolites of -shogaol were detected in urine collected from human after drinking ginger tea, using LC/ESI-MS/MS. Our results clearly indicate the mercapturic acid pathway is a major metabolic route for -shogaol in mice and for shogaols in human. Furthermore, we also investigated the regulation of glutathione (GSH) by -shogaol in human colon cancer cells HCT-116. Our results show -shogaol, after initially depleting glutathione levels, can subsequently restore and increase GSH levels over time.
Shogaols are metabolized extensively in mouse and human to form thiol-conjugated metabolites and GSH might play an important role in the cancer-preventive activity of ginger.