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Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol

Although resveratrol (RES) is barely detectable in the plasma and tissues upon oral consumption, collective evidence reveals that RES presents various bioactivities in vivo, including anti-inflammation and anti-cancer. This paradox necessitates further research on profiling and characterizing the bi...

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Autores principales: Li, Fang, Han, Yanhui, Wu, Xian, Cao, Xiaoqiong, Gao, Zili, Sun, Yue, Wang, Minqi, Xiao, Hang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131081/
https://www.ncbi.nlm.nih.gov/pubmed/35634412
http://dx.doi.org/10.3389/fnut.2022.912591
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author Li, Fang
Han, Yanhui
Wu, Xian
Cao, Xiaoqiong
Gao, Zili
Sun, Yue
Wang, Minqi
Xiao, Hang
author_facet Li, Fang
Han, Yanhui
Wu, Xian
Cao, Xiaoqiong
Gao, Zili
Sun, Yue
Wang, Minqi
Xiao, Hang
author_sort Li, Fang
collection PubMed
description Although resveratrol (RES) is barely detectable in the plasma and tissues upon oral consumption, collective evidence reveals that RES presents various bioactivities in vivo, including anti-inflammation and anti-cancer. This paradox necessitates further research on profiling and characterizing the biotransformation of RES, as its metabolites may contribute profound biological effects. After 4-week oral administration, 11 metabolites of RES were identified and quantified in mice by HPLC-MS/MS, including dihydro-resveratrol (DHR), lunularin (LUN), and conjugates (sulfates and glucuronides) of RES, DHR and LUN. Importantly, DHR, LUN, and their conjugates were much more abundantly distributed in tissues, gastrointestinal tract (GIT), and biological fluids compared to RES and its conjugates. Moreover, we established that DHR and LUN were gut bacteria-derived metabolites of RES, as indicated by their depletion in antibiotic-treated mice. Furthermore, the biological activities of RES, DHR, and LUN were determined at physiologically relevant levels. DHR and LUN exhibited stronger anti-inflammatory and anti-cancer effects than RES at the concentrations found in mouse tissues. In summary, our study profiled the tissue distribution of the metabolites of RES after its oral administration in mice and uncovered the important role of gut microbial metabolites of RES in the biological activities of RES in vivo.
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spelling pubmed-91310812022-05-26 Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol Li, Fang Han, Yanhui Wu, Xian Cao, Xiaoqiong Gao, Zili Sun, Yue Wang, Minqi Xiao, Hang Front Nutr Nutrition Although resveratrol (RES) is barely detectable in the plasma and tissues upon oral consumption, collective evidence reveals that RES presents various bioactivities in vivo, including anti-inflammation and anti-cancer. This paradox necessitates further research on profiling and characterizing the biotransformation of RES, as its metabolites may contribute profound biological effects. After 4-week oral administration, 11 metabolites of RES were identified and quantified in mice by HPLC-MS/MS, including dihydro-resveratrol (DHR), lunularin (LUN), and conjugates (sulfates and glucuronides) of RES, DHR and LUN. Importantly, DHR, LUN, and their conjugates were much more abundantly distributed in tissues, gastrointestinal tract (GIT), and biological fluids compared to RES and its conjugates. Moreover, we established that DHR and LUN were gut bacteria-derived metabolites of RES, as indicated by their depletion in antibiotic-treated mice. Furthermore, the biological activities of RES, DHR, and LUN were determined at physiologically relevant levels. DHR and LUN exhibited stronger anti-inflammatory and anti-cancer effects than RES at the concentrations found in mouse tissues. In summary, our study profiled the tissue distribution of the metabolites of RES after its oral administration in mice and uncovered the important role of gut microbial metabolites of RES in the biological activities of RES in vivo. Frontiers Media S.A. 2022-05-11 /pmc/articles/PMC9131081/ /pubmed/35634412 http://dx.doi.org/10.3389/fnut.2022.912591 Text en Copyright © 2022 Li, Han, Wu, Cao, Gao, Sun, Wang and Xiao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Li, Fang
Han, Yanhui
Wu, Xian
Cao, Xiaoqiong
Gao, Zili
Sun, Yue
Wang, Minqi
Xiao, Hang
Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol
title Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol
title_full Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol
title_fullStr Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol
title_full_unstemmed Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol
title_short Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol
title_sort gut microbiota-derived resveratrol metabolites, dihydroresveratrol and lunularin, significantly contribute to the biological activities of resveratrol
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131081/
https://www.ncbi.nlm.nih.gov/pubmed/35634412
http://dx.doi.org/10.3389/fnut.2022.912591
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