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Metabolism of flavonolignans in human hepatocytes
J. Vrba, B. Papoušková, L. Roubalová, M. Zatloukalová, D. Biedermann, V. Křen, K. Valentová, J. Ulrichová, J. Vacek,
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
- MeSH
- biotransformace fyziologie MeSH
- dospělí MeSH
- flavonolignany metabolismus MeSH
- hepatocyty metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- silymarin analogy a deriváty metabolismus MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
This study examined the in vitro biotransformation of eight structurally related flavonolignans, namely silybin, 2,3-dehydrosilybin, silychristin, 2,3-dehydrosilychristin, silydianin, 2,3-dehydrosilydianin, isosilybin A and isosilybin B. The metabolic transformations were performed using primary cultures of human hepatocytes and recombinant human cytochromes P450 (CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4). The metabolites produced were analyzed by ultra-performance liquid chromatography coupled with tandem mass spectrometry. We found that each of the tested compounds was metabolized in vitro by one or more CYP enzymes, which catalyzed O-demethylation, hydroxylation, hydrogenation and dehydrogenation reactions. In human hepatocytes, silybin, 2,3-dehydrosilybin, silychristin, 2,3-dehydrosilychristin, and isosilybins A and B were directly conjugated by sulfation or glucuronidation. Moreover, isosilybin A was also converted to a methyl derivative, while isosilybin B was hydroxylated and methylated. Silydianin and 2,3-dehydrosilydianin were found to undergo hydrogenation and/or glucuronidation. In addition, 2,3-dehydrosilydianin was found to be metabolically the least stable flavonolignan in human hepatocytes, and its main metabolite was a cleavage product corresponding to a loss of CO. We conclude that the hepatic biotransformation of flavonolignans primarily involves the phase II conjugation reactions, however in some cases the phase I reactions may also occur. These results are highly relevant for research focused on flavonolignan metabolism and pharmacology.
Citace poskytuje Crossref.org
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- $a Vrba, Jiří $u Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic.
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- $a Metabolism of flavonolignans in human hepatocytes / $c J. Vrba, B. Papoušková, L. Roubalová, M. Zatloukalová, D. Biedermann, V. Křen, K. Valentová, J. Ulrichová, J. Vacek,
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- $a This study examined the in vitro biotransformation of eight structurally related flavonolignans, namely silybin, 2,3-dehydrosilybin, silychristin, 2,3-dehydrosilychristin, silydianin, 2,3-dehydrosilydianin, isosilybin A and isosilybin B. The metabolic transformations were performed using primary cultures of human hepatocytes and recombinant human cytochromes P450 (CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4). The metabolites produced were analyzed by ultra-performance liquid chromatography coupled with tandem mass spectrometry. We found that each of the tested compounds was metabolized in vitro by one or more CYP enzymes, which catalyzed O-demethylation, hydroxylation, hydrogenation and dehydrogenation reactions. In human hepatocytes, silybin, 2,3-dehydrosilybin, silychristin, 2,3-dehydrosilychristin, and isosilybins A and B were directly conjugated by sulfation or glucuronidation. Moreover, isosilybin A was also converted to a methyl derivative, while isosilybin B was hydroxylated and methylated. Silydianin and 2,3-dehydrosilydianin were found to undergo hydrogenation and/or glucuronidation. In addition, 2,3-dehydrosilydianin was found to be metabolically the least stable flavonolignan in human hepatocytes, and its main metabolite was a cleavage product corresponding to a loss of CO. We conclude that the hepatic biotransformation of flavonolignans primarily involves the phase II conjugation reactions, however in some cases the phase I reactions may also occur. These results are highly relevant for research focused on flavonolignan metabolism and pharmacology.
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- $a Papoušková, Barbora $u Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacký University, 17. listopadu 12, Olomouc 77146, Czech Republic.
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- $a Roubalová, Lenka $u Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic.
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- $a Zatloukalová, Martina $u Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic.
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- $a Biedermann, David $u Institute of Microbiology of the Czech Academy of Sciences, Laboratory of Biotransformation, Vídeňská 1083, Prague 14220, Czech Republic.
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- $a Ulrichová, Jitka $u Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic.
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- $a Vacek, Jan $u Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic. Electronic address: jan.vacek@upol.cz.
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