Metabolism of ginger component [6]-shogaol in liver microsomes from mouse, rat, dog, monkey, and human
| Autor: | Dominique N. Soroka, Shengmin Sang, Yingdong Zhu, Huadong Chen |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Magnetic Resonance Spectroscopy
Aldo-Keto Reductases Catechols Oxidative phosphorylation Ginger Pharmacology Reductase Biology Chemoprevention Biochemistry Article Gas Chromatography-Mass Spectrometry Rats Sprague-Dawley Mice chemistry.chemical_compound Dogs Cytochrome P-450 Enzyme System Aldehyde Reductase Cell Line Tumor Genetics Animals Cytochrome P-450 Enzyme Inhibitors Humans Molecular Biology Liver microsomes Chromatography High Pressure Liquid Aldo-keto reductase Plant Extracts Component (thermodynamics) Haplorhini Shogaol Metabolism Triazoles Rats Alcohol Oxidoreductases chemistry Apoptosis Microsomes Liver Microsome Glycyrrhetinic Acid Growth inhibition Food Science Biotechnology |
| Zdroj: | Molecular Nutrition & Food Research. 57:865-876 |
| ISSN: | 1613-4125 |
| DOI: | 10.1002/mnfr.201200708 |
| Popis: | Scope 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. Methods and 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. Conclusion 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. |
| Databáze: | OpenAIRE |
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