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Detection and structural characterization of the metabolites of dihydroresveratrol in rats by liquid chromatography coupled to high‐resolution tandem mass spectrometry

Rationale Dihydroresveratrol has been demonstrated to possess a wide spectrum of bioactivities, such as anti‐oxidant and anti‐inflammatory effects. The aim of the present study was to investigate the metabolic profiles of dihydroresveratrol in rats. Methods The in vitro metabolism was elucidated by...

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Published in:Rapid communications in mass spectrometry 2021-02, Vol.35 (4), p.e8991-n/a
Main Authors: Ji, Qiang‐Guo, Ma, Ming‐Hua, Hu, Xue‐Mei, Zhang, Yi‐Jun, Xu, Xiao‐Hong, Nian, Hua
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Ma, Ming‐Hua
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description Rationale Dihydroresveratrol has been demonstrated to possess a wide spectrum of bioactivities, such as anti‐oxidant and anti‐inflammatory effects. The aim of the present study was to investigate the metabolic profiles of dihydroresveratrol in rats. Methods The in vitro metabolism was elucidated by incubating dihydroresveratrol with rat hepatocytes for 2 h at 37°C. For in vivo metabolism, dihydroresveratrol was orally administered to rats at a single dose of 50 mg/kg and the resulting biliary and urinary samples were collected. All the samples were analyzed by liquid chromatography combined with electrospray ionization high‐resolution mass spectrometry. The structures of the metabolites were proposed based on their accurate masses and their MS/MS product ions. Results A total of 16 metabolites including three phase I metabolites and 13 phase II metabolites were detected and structurally proposed. Among these metabolites, M6 and M14 were unambiguously identified as 3′‐hydroxylresveratrol and resveratrol, respectively, using reference standards. Dihydroresveratrol was mainly metabolized into resveratrol (M14) and a glucuronide conjugate (M12), which were excreted into urine and bile as the major metabolites. Conclusions The metabolic pathways of dihydroresveratrol involved hydroxylation, dehydrogenation, glucuronidation, glutathione (GSH) conjugation and methylation. The present study provided useful information with regard to the metabolic profiles of dihydroresveratrol in rats.
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The aim of the present study was to investigate the metabolic profiles of dihydroresveratrol in rats. Methods The in vitro metabolism was elucidated by incubating dihydroresveratrol with rat hepatocytes for 2 h at 37°C. For in vivo metabolism, dihydroresveratrol was orally administered to rats at a single dose of 50 mg/kg and the resulting biliary and urinary samples were collected. All the samples were analyzed by liquid chromatography combined with electrospray ionization high‐resolution mass spectrometry. The structures of the metabolites were proposed based on their accurate masses and their MS/MS product ions. Results A total of 16 metabolites including three phase I metabolites and 13 phase II metabolites were detected and structurally proposed. Among these metabolites, M6 and M14 were unambiguously identified as 3′‐hydroxylresveratrol and resveratrol, respectively, using reference standards. Dihydroresveratrol was mainly metabolized into resveratrol (M14) and a glucuronide conjugate (M12), which were excreted into urine and bile as the major metabolites. Conclusions The metabolic pathways of dihydroresveratrol involved hydroxylation, dehydrogenation, glucuronidation, glutathione (GSH) conjugation and methylation. The present study provided useful information with regard to the metabolic profiles of dihydroresveratrol in rats.</description><identifier>ISSN: 0951-4198</identifier><identifier>EISSN: 1097-0231</identifier><identifier>DOI: 10.1002/rcm.8991</identifier><identifier>PMID: 33125777</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Chromatography ; Conjugation ; Dehydrogenation ; Glutathione ; Hydroxylation ; In vitro methods and tests ; Ions ; Liquid chromatography ; Mass spectrometry ; Metabolism ; Metabolites ; Methylation ; Oxidizing agents ; Scientific imaging ; Spectroscopy ; Structural analysis</subject><ispartof>Rapid communications in mass spectrometry, 2021-02, Vol.35 (4), p.e8991-n/a</ispartof><rights>2020 John Wiley &amp; Sons Ltd</rights><rights>2020 John Wiley &amp; Sons Ltd.</rights><rights>2021 John Wiley &amp; Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3491-a8f930356e4c370c819540b59babede9d1a32e704cc2023d1b246b6134bb9a593</citedby><cites>FETCH-LOGICAL-c3491-a8f930356e4c370c819540b59babede9d1a32e704cc2023d1b246b6134bb9a593</cites><orcidid>0000-0002-6736-0401</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33125777$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ji, Qiang‐Guo</creatorcontrib><creatorcontrib>Ma, Ming‐Hua</creatorcontrib><creatorcontrib>Hu, Xue‐Mei</creatorcontrib><creatorcontrib>Zhang, Yi‐Jun</creatorcontrib><creatorcontrib>Xu, Xiao‐Hong</creatorcontrib><creatorcontrib>Nian, Hua</creatorcontrib><title>Detection and structural characterization of the metabolites of dihydroresveratrol in rats by liquid chromatography coupled to high‐resolution tandem mass spectrometry</title><title>Rapid communications in mass spectrometry</title><addtitle>Rapid Commun Mass Spectrom</addtitle><description>Rationale Dihydroresveratrol has been demonstrated to possess a wide spectrum of bioactivities, such as anti‐oxidant and anti‐inflammatory effects. The aim of the present study was to investigate the metabolic profiles of dihydroresveratrol in rats. Methods The in vitro metabolism was elucidated by incubating dihydroresveratrol with rat hepatocytes for 2 h at 37°C. For in vivo metabolism, dihydroresveratrol was orally administered to rats at a single dose of 50 mg/kg and the resulting biliary and urinary samples were collected. All the samples were analyzed by liquid chromatography combined with electrospray ionization high‐resolution mass spectrometry. The structures of the metabolites were proposed based on their accurate masses and their MS/MS product ions. Results A total of 16 metabolites including three phase I metabolites and 13 phase II metabolites were detected and structurally proposed. Among these metabolites, M6 and M14 were unambiguously identified as 3′‐hydroxylresveratrol and resveratrol, respectively, using reference standards. Dihydroresveratrol was mainly metabolized into resveratrol (M14) and a glucuronide conjugate (M12), which were excreted into urine and bile as the major metabolites. Conclusions The metabolic pathways of dihydroresveratrol involved hydroxylation, dehydrogenation, glucuronidation, glutathione (GSH) conjugation and methylation. 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Dihydroresveratrol was mainly metabolized into resveratrol (M14) and a glucuronide conjugate (M12), which were excreted into urine and bile as the major metabolites. Conclusions The metabolic pathways of dihydroresveratrol involved hydroxylation, dehydrogenation, glucuronidation, glutathione (GSH) conjugation and methylation. The present study provided useful information with regard to the metabolic profiles of dihydroresveratrol in rats.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33125777</pmid><doi>10.1002/rcm.8991</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-6736-0401</orcidid></addata></record>
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subjects Chromatography
Conjugation
Dehydrogenation
Glutathione
Hydroxylation
In vitro methods and tests
Ions
Liquid chromatography
Mass spectrometry
Metabolism
Metabolites
Methylation
Oxidizing agents
Scientific imaging
Spectroscopy
Structural analysis
title Detection and structural characterization of the metabolites of dihydroresveratrol in rats by liquid chromatography coupled to high‐resolution tandem mass spectrometry
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