{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:16:52Z","timestamp":1790979412562,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T00:00:00Z","timestamp":1513036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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\u2032-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.<\/jats:p>","DOI":"10.3390\/nu9121347","type":"journal-article","created":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T13:35:00Z","timestamp":1513085700000},"page":"1347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Involvement of UDP-Glucuronosyltransferases and Sulfotransferases in the Excretion and Tissue Distribution of Resveratrol in Mice"],"prefix":"10.3390","volume":"9","author":[{"given":"Michaela","family":"B\u00f6hmdorfer","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Division of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna 1010, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akos","family":"Szakmary","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Vienna 1010, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Schiestl","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Vienna 1010, Austria"},{"name":"Department of Pathology and Lab Medicine, UCLA School of Medicine and School of Public Health, University of California at Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Vaquero","sequence":"additional","affiliation":[{"name":"Saint-Antoine Research Center, Sorbonne University, Paris 75005, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Riha","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Division of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna 1010, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Division of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna 1010, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresia","family":"Thalhammer","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Medical University of Vienna, Vienna 1010, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Szekeres","sequence":"additional","affiliation":[{"name":"Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna 1010, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"J\u00e4ger","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Division of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna 1010, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrd2060","article-title":"Therapeutic potential of resveratrol: The in vivo evidence","volume":"6","author":"Baur","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5277","DOI":"10.2174\/1381612821666150928155612","article-title":"Reviewing the role of resveratrol as a natural modulator of microglial activities","volume":"21","author":"Porro","year":"2015","journal-title":"Curr. Pharm. Des."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6726","DOI":"10.2174\/1381612811319380005","article-title":"Resveratrol: New avenues for a natural compound in neuroprotection","volume":"19","author":"Porquet","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1124\/dmd.104.000885","article-title":"High absorption but very low bioavailability of oral resveratrol in humans","volume":"32","author":"Walle","year":"2004","journal-title":"Drug Metab. Dispos."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1124\/jpet.102.033340","article-title":"Metabolism and disposition of resveratrol in rats: Extent of absorption, glucuronidation, and enterohepatic recirculation evidenced by a linked-rat model","volume":"302","author":"Marier","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/mnfr.200700290","article-title":"Quantification of free and protein-bound trans-resveratrol metabolites and identification of trans-resveratrol-C\/O-conjugated diglucuronides-two novel resveratrol metabolites in human plasma","volume":"52","author":"Burkon","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7392","DOI":"10.1158\/0008-5472.CAN-10-2027","article-title":"Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients","volume":"70","author":"Patel","year":"2010","journal-title":"Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1021\/jf030582e","article-title":"Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice","volume":"52","author":"Meng","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1002\/mnfr.201100140","article-title":"Metabolites and tissue distribution of resveratrol in the pig","volume":"55","author":"Vallejo","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1002\/jps.21057","article-title":"Metabolism and disposition of resveratrol in the isolated perfused rat liver: Role of Mrp2 in the biliary excretion of glucuronides","volume":"97","author":"Hagenauer","year":"2008","journal-title":"J. Pharm. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/mnfr.201200589","article-title":"Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans","volume":"58","author":"Cottart","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.phrs.2012.08.001","article-title":"Pharmacokinetics of resveratrol metabolic profile in healthy humans after moderate consumption of red wine and grape extract tablets","volume":"66","author":"Estruch","year":"2012","journal-title":"Pharmacol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jep.2012.10.009","article-title":"Pharmacokinetics and tissue distribution of resveratrol, emodin and their metabolites after intake of Polygonum cuspidatum in rats","volume":"144","author":"Lin","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.phymed.2012.12.012","article-title":"Pharmacokinetics, tissue distribution and excretion study of resveratrol and its Prodrug 3,5,4\u2032-tri-O-acetylresveratrol in rats","volume":"20","author":"Liang","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.canlet.2009.08.020","article-title":"Expression of sulfotransferases and sulfatases in human breast cancer: Impact on resveratrol metabolism","volume":"289","author":"Miksits","year":"2010","journal-title":"Cancer Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1080\/00498250500354253","article-title":"Sulfation of resveratrol in human liver: Evidence of a major role for the sulfotransferases SULT1A1 and SULT1E1","volume":"35","author":"Miksits","year":"2005","journal-title":"Xenobiotica"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1211\/jpp.58.4.0006","article-title":"Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms","volume":"58","author":"Brill","year":"2006","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1006\/abbi.2001.2496","article-title":"Regioselective and stereospecific glucuronidation of trans- and cis-resveratrol in human","volume":"393","author":"Aumont","year":"2001","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_19","first-page":"324","article-title":"The effect of organic anion-transporting polypeptides 1B1, 1B3 and 2B1 on the antitumor activity of flavopiridol in breast cancer cells","volume":"58","author":"Riha","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1124\/dmd.106.012070","article-title":"Tissue- and gender-specific mRNA expression of UDP-glucuronosyltransferases (UGTs) in mice","volume":"35","author":"Buckley","year":"2007","journal-title":"Drug Metab. Dispos."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1124\/dmd.112.050211","article-title":"RNA-sequencing quantification of hepatic ontogeny and tissue distribution of mRNAs of phase II enzymes in mice","volume":"41","author":"Lu","year":"2013","journal-title":"Drug Metab. Dispos."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1021\/acs.molpharmaceut.7b00435","article-title":"Profiles and Gender-Specifics of UDP-Glucuronosyltransferases and Sulfotransferases Expressions in the Major Metabolic Organs of Wild-Type and Efflux Transporter Knockout FVB Mice","volume":"14","author":"Chen","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1093\/bioinformatics\/bth349","article-title":"Java Treeview-extensible visualization of microarray data","volume":"20","author":"Saldanha","year":"2004","journal-title":"Bioinformatics"},{"key":"ref_24","first-page":"2107","article-title":"Increased transport of resveratrol across monolayers of the human intestinal Caco-2 cells is mediated by inhibition and saturation of metabolites","volume":"9","author":"Hagenauer","year":"2006","journal-title":"Pharm. Res."},{"key":"ref_25","first-page":"466","article-title":"Species and sex differences in propofol glucuronidation in liver microsomes of humans, monkeys, rats and mice","volume":"70","author":"Mukai","year":"2015","journal-title":"Pharmazie"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/bdd.1989","article-title":"Species- and gender-dependent differences in the glucuronidation of a flavonoid glucoside and its aglycone determined using expressed UGT enzymes and microsomes","volume":"36","author":"Dai","year":"2015","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3109\/10408444.2012.674100","article-title":"Ontogeny of mammalian metabolizing enzymes in humans and animals used in toxicological studies","volume":"42","author":"Saghir","year":"2012","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.brainres.2015.07.005","article-title":"Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders","volume":"1628","author":"Qosa","year":"2015","journal-title":"Brain Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1124\/mol.108.052019","article-title":"Intestinal breast cancer resistance protein (BCRP)\/Bcrp1 and multidrug resistance protein 3 (MRP3)\/Mrp3 are involved in the pharmacokinetics of resveratrol","volume":"75","author":"Burkon","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1124\/dmd.108.020859","article-title":"Closing the gaps: A full scan of the intestinal expression of p-glycoprotein, breast cancer resistance protein, and multidrug resistance-associated protein 2 in male and female rats","volume":"36","author":"MacLean","year":"2008","journal-title":"Drug Metab. Dispos."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Menet, M.C., Baron, S., Taghi, M., Diestra, R., Darg\u00e8re, D., Lapr\u00e9vote, O., Nivet-Antoine, V., Beaudeux, J.L., B\u00e9darida, T., and Cottart, C.H. (2017). Distribution of trans-resveratrol and its metabolites after acute or sustained administration in mouse heart, brain, and liver. Mol. Nutr. Food Res., 61.","DOI":"10.1002\/mnfr.201600686"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jpba.2009.03.026","article-title":"Quantification of trans-resveratrol and its metabolites in rat plasma and tissues by HPLC","volume":"51","author":"Juan","year":"2010","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jpba.2014.01.039","article-title":"Simultaneous quantification of trans-resveratrol and its sulfate and glucuronide metabolites in rat tissues by stable isotope-dilution UPLC-MS\/MS analysis","volume":"94","author":"Lou","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"364","DOI":"10.2133\/dmpk.DMPK-11-RG-006","article-title":"Hepatic glucuronidation of resveratrol: Interspecies comparison of enzyme kinetic profiles in human, mouse, rat, and dog","volume":"26","author":"Thalhammer","year":"2011","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1124\/jpet.117.240382","article-title":"Comprehensive characterization of mouse UDP-glucuronosyltransferase (Ugt) belonging to the Ugt2b subfamily: Identification of Ugt2b36 as the predominant isoform involved in morphine glucuronidation","volume":"361","author":"Kurita","year":"2017","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_36","unstructured":"Gene Cards\u00ae: The Human Gene Database. Available online: www.genecards.org."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/oxfordjournals.jbchem.a022097","article-title":"Molecular cloning, expression, and characterization of a novel mouse liver SULT1B1 sulfotransferase","volume":"124","author":"Saeki","year":"1998","journal-title":"J. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1002\/mnfr.201100117","article-title":"Enhancing the bioavailability of resveratrol by combining it with piperine","volume":"55","author":"Johnson","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1021\/mp5005838","article-title":"Involvement of the inhibition of intestinal glucuronidation in enhancing the oral bioavailability of resveratrol by labrasol containing nanoemulsions","volume":"12","author":"Zhou","year":"2015","journal-title":"Mol. Pharm."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/12\/1347\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:53:36Z","timestamp":1760208816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/12\/1347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,12]]},"references-count":39,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["nu9121347"],"URL":"https:\/\/doi.org\/10.3390\/nu9121347","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,12]]}}}