title: Metabolism of ginger component [6]-shogaol in liver microsomes from mouse, rat, dog, monkey, and human.
abstract: METHODS
  There are limited data on the metabolism of [6]-shogaol (6S), a major bioactive component of ginger. This study demonstrates metabolism of 6S in liver microsomes from mouse, rat, dog, monkey, and human.
  
  
  RESULTS
  The in vitro metabolism of 6S was compared among five species using liver microsomes from mouse, rat, dog, monkey, and human. Following incubations with 6S, three major reductive metabolites 1-(4'-hydroxy-3'-methoxyphenyl)-4-decen-3-ol (M6), 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol (M9), and 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M11), as well as two new oxidative metabolites (1E,4E)-1-(4'-hydroxy-3'-methoxyphenyl)-deca-1,4-dien-3-one (M14) and (E)-1-(4'-hydroxy-3'-methoxyphenyl)-dec-1-en-3-one (M15) were found in all species. The kinetic parameters of M6 in liver microsomes from each respective species were quantified using Michaelis-Menten theory. A broad CYP-450 inhibitor, 1-aminobenzotriazole, precluded the formation of oxidative metabolites, M14 and M15, and 18β-glycyrrhetinic acid, an aldo-keto reductase inhibitor, eradicated the formation of the reductive metabolites M6, M9, and M11 in all species. Metabolites M14 and M15 were tested for cancer cell growth inhibition and induction of apoptosis and both showed substantial activity, with M14 displaying greater potency than 6S.
  
  
  CONCLUSIONS
  We conclude that 6S is metabolized extensively in mammalian species mouse, rat, dog, monkey, and human, and that there are significant interspecies differences to consider when planning preclinical trials toward 6S chemoprevention.
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
authors: D
authors: Soroka
authors: Yingdong
authors: Y
authors: Zhu
authors: Shengmin
authors: S
authors: Sang
mesh_terms: D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D000818:Animals; D002396:Catechols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018890:Chemoprevention; D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004285:Dogs; D008401:Gas Chromatography-Mass Spectrometry; D020939:Zingiber officinale / Q000737:chemistry*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000882:Haplorhini; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology
chemical_list: D002396:Catechols; D065607:Cytochrome P-450 Enzyme Inhibitors; D010936:Plant Extracts; D014230:Triazoles; C119129:18alpha-glycyrrhetinic acid; C033020:1-aminobenzotriazole; C040115:shogaol; D003577:Cytochrome P-450 Enzyme System; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; C000614209:AKR7A5 protein, mouse; D006034:Glycyrrhetinic Acid