title: Characterization of thiol-conjugated metabolites of ginger components shogaols in mouse and human urine and modulation of the glutathione levels in cancer cells by [6]-shogaol.
abstract: METHODS
  Shogaols, a series of major constituents in dried ginger with the most abundant being [6]-, [8]-, and [10]-shogaols, show much higher anticancer potencies than gingerols. Previously, we reported the mercapturic acid pathway as a major metabolic route for [6]-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.
  
  
  RESULTS
  We first investigate the metabolism of [10]-shogaol in mouse urine, and then investigate the biotransformation of shogaols in human urine. Our results show that eight major thiol-conjugated metabolites of [10]-shogaol were detected in mouse urine, while six major thiol-conjugated metabolites of [6]-shogaol, two thiol-conjugated metabolites of [8]-shogaol, and two thiol-conjugated metabolites of [10]-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 [10]-shogaol in mice and for shogaols in human. Furthermore, we also investigated the regulation of glutathione (GSH) by [6]-shogaol in human colon cancer cells HCT-116. Our results show [6]-shogaol, after initially depleting glutathione levels, can subsequently restore and increase GSH levels over time.
  
  
  CONCLUSIONS
  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.
authors: Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, NC, USA.
authors: Huadong
authors: H
authors: Chen
authors: Dominique N
authors: DN
authors: Soroka
authors: Yuhui
authors: Y
authors: Hu
authors: Xiaoxin
authors: X
authors: Chen
authors: Shengmin
authors: S
authors: Sang
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000328:Adult; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001628:Beverages; D002396:Catechols / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine*; D045744:Cell Line, Tumor; D005260:Female; D020939:Zingiber officinale / Q000737:chemistry* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006139:Guaiacol / Q000031:analogs & derivatives / Q000737:chemistry / Q000652:urine; D045325:HCT116 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000652:urine; D053719:Tandem Mass Spectrometry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002396:Catechols; D013438:Sulfhydryl Compounds; D006139:Guaiacol; C040115:shogaol; C585131:(8)-shogaol; D005978:Glutathione; C585130:(10)-shogaol; D000111:Acetylcysteine