title: Metabolism of [6]-shogaol in mice and in cancer cells.
abstract: Ginger has received extensive attention because of its antioxidant, anti-inflammatory, and antitumor activities. However, the metabolic fate of its major components is still unclear. In the present study, the metabolism of [6]-shogaol, one of the major active components in ginger, was examined for the first time in mice and in cancer cells. Thirteen metabolites were detected and identified, seven of which were purified from fecal samples collected from [6]-shogaol-treated mice. Their structures were elucidated as 1-(4'-hydroxy-3'-methoxyphenyl)-4-decen-3-ol (M6), 5-methoxy-1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M7), 3',4'-dihydroxyphenyl-decan-3-one (M8), 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol (M9), 5-methylthio-1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M10), 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M11), and 5-methylthio-1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol (M12) on the basis of detailed analysis of their (1)H, (13)C, and two-dimensional NMR data. The rest of the metabolites were identified as 5-cysteinyl-M6 (M1), 5-cysteinyl-[6]-shogaol (M2), 5-cysteinylglycinyl-M6 (M3), 5-N-acetylcysteinyl-M6 (M4), 5-N-acetylcysteinyl-[6]-shogaol (M5), and 5-glutathiol-[6]-shogaol (M13) by analysis of the MS(n) (n = 1-3) spectra and comparison to authentic standards. Among the metabolites, M1 through M5, M10, M12, and M13 were identified as the thiol conjugates of [6]-shogaol and its metabolite M6. M9 and M11 were identified as the major metabolites in four different cancer cell lines (HCT-116, HT-29, H-1299, and CL-13), and M13 was detected as a major metabolite in HCT-116 human colon cancer cells. We further showed that M9 and M11 are bioactive compounds that can inhibit cancer cell growth and induce apoptosis in human cancer cells. Our results suggest that 1) [6]-shogaol is extensively metabolized in these two models, 2) its metabolites are bioactive compounds, and 3) the mercapturic acid pathway is one of the major biotransformation pathways of [6]-shogaol.
authors.affiliation: Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC 28081, USA.
authors.forename: Huadong
authors.initials: H
authors.lastname: Chen
authors.forename: Lishuang
authors.initials: L
authors.lastname: Lv
authors.forename: Dominique
authors.initials: D
authors.lastname: Soroka
authors.forename: Renaud F
authors.initials: RF
authors.lastname: Warin
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Parks
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Hu
authors.forename: Yingdong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Chen
authors.forename: Shengmin
authors.initials: S
authors.lastname: Sang
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001711:Biotransformation; D002396:Catechols / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D005260:Female; D020939:Zingiber officinale / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D016588:Anticarcinogenic Agents; D002396:Catechols; D010936:Plant Extracts; C040115:shogaol