Abstract
Resveratrol is a naturally occurring polyphenolic compound with various pharmacological activities. It is unknown whether the expression of metabolizing enzymes correlates with resveratrol levels in organs and tissues. Therefore, we investigated the metabolism and tissue distribution of resveratrol in mice and assessed its association with the expression of UDP-glucuronosyltransferase (Ugt) and sulfotransferase (Sult) genes. Plasma, urine, feces, and various organs were analyzed using high-performance liquid chromatography at up to 8 h after intragastric resveratrol administration. The metabolism of resveratrol was pronounced, leading to the formation of resveratrol glucuronides and sulfates. Concentrations of resveratrol and its metabolites were high in the gastrointestinal organs, urine, and feces, but low in the liver and kidneys. In lung, heart, thymus, and brain tissues, parent resveratrol levels exceeded the sulfate and glucuronide concentrations. The formation of resveratrol conjugates correlated with the expression of certain Ugt and Sult genes. Reverse transcription quantitative PCR (RT-qPCR) analysis revealed high mRNA expression of Ugt1a1 and Ugt1a6a in the liver, duodenum, jejunum, ileum, and colon, leading to high concentrations of resveratrol-3-O-glucuronide in these organs. Strong correlations of resveratrol-3-O-sulfate and resveratrol-3-O-4′-O-disulfate formation with Sult1a1 mRNA expression were also observed, particularly in the liver and colon. In summary, our data revealed organ-specific expression of Sults and Ugts in mice that strongly affects resveratrol concentrations; this may also be predictive in humans following oral uptake of dietary resveratrol.
Highlights
IntroductionResveratrol (3,40 ,5-trihydroxy-trans-stilbene) is a naturally occurring compound that is produced by a wide variety of plants, berries, and fruits, and is mainly found in the skin of grapes and in red Nutrients 2017, 9, 1347; doi:10.3390/nu9121347 www.mdpi.com/journal/nutrients NutrientsResveratrol (3,4′,5-trihydroxy-trans-stilbene) is a naturally occurring compound that is produced by a wide ofin plants, berries,has andincreased fruits, and is mainly found in thereporting skin of grapes andininimproving red wine [1]. wine [1].varietyInterest resveratrol due to various studies its role the Interest inofresveratrol has increased due to various studies its role in improving the outcomes outcomes various pathologies, e.g., cardiovascular andreporting neurodegenerative diseases, inflammation, of various pathologies, e.g., cardiovascular and neurodegenerative diseases, inflammation, viral viral infections, and cancer [2,3,4].These beneficial effects on health are observed despite extremely infections, and cancerThese beneficial effects on health are observed despite extremely lowin low bioavailability and rapid clearance from the circulation [4,5], based on extensive metabolism bioavailability and rapid clearance from the circulation [4,5], on extensive metabolism humans humans and animal models [6,7,8,9]
The results indicate that resveratrol and its metabolites were rapidly and widely distributed in the body
In accordance with previous data on the differences in Ugt and Sult expression in mouse organs [20,21,22], we identified organ-specific expression of different isoforms
Summary
Resveratrol (3,40 ,5-trihydroxy-trans-stilbene) is a naturally occurring compound that is produced by a wide variety of plants, berries, and fruits, and is mainly found in the skin of grapes and in red Nutrients 2017, 9, 1347; doi:10.3390/nu9121347 www.mdpi.com/journal/nutrients NutrientsResveratrol (3,4′,5-trihydroxy-trans-stilbene) is a naturally occurring compound that is produced by a wide ofin plants, berries,has andincreased fruits, and is mainly found in thereporting skin of grapes andininimproving red wine [1]. wine [1].varietyInterest resveratrol due to various studies its role the Interest inofresveratrol has increased due to various studies its role in improving the outcomes outcomes various pathologies, e.g., cardiovascular andreporting neurodegenerative diseases, inflammation, of various pathologies, e.g., cardiovascular and neurodegenerative diseases, inflammation, viral viral infections, and cancer [2,3,4].These beneficial effects on health are observed despite extremely infections, and cancerThese beneficial effects on health are observed despite extremely lowin low bioavailability and rapid clearance from the circulation [4,5], based on extensive metabolism bioavailability and rapid clearance from the circulation [4,5], on extensive metabolism humans humans and animal models [6,7,8,9]. Resveratrol (3,40 ,5-trihydroxy-trans-stilbene) is a naturally occurring compound that is produced by a wide variety of plants, berries, and fruits, and is mainly found in the skin of grapes and in red Nutrients 2017, 9, 1347; doi:10.3390/nu9121347 www.mdpi.com/journal/nutrients Nutrients. Resveratrol (3,4′,5-trihydroxy-trans-stilbene) is a naturally occurring compound that is produced by a wide ofin plants, berries,has andincreased fruits, and is mainly found in thereporting skin of grapes andininimproving red wine [1]. Interest resveratrol due to various studies its role the Interest inofresveratrol has increased due to various studies its role in improving the outcomes outcomes various pathologies, e.g., cardiovascular andreporting neurodegenerative diseases, inflammation, of various pathologies, e.g., cardiovascular and neurodegenerative diseases, inflammation, viral viral infections, and cancer [2,3,4]. Sulfation and glucuronidation of resveratrol sulfotransferases resveratrolare arecarried carriedout outby byUDP-glucuronosyltransferases
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