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.
The polyphenol trans-resveratrol (t-RES) is present as t-RES-3-O-beta-D-glycoside, termed piceid, in several plant-derived foods. Although data on the metabolism and on in vivo effects of t-RES have been reported, quantitative data on the metabolites formed after dietary intake of t-RES or piceid are still lacking. In this study, 85.5 mg of piceid per 70 kg of body weight (bw) were administered to healthy volunteers in a bolus dose. t-RES metabolites formed in plasma and urine were identified and quantified by LC-MS/MS, NMR, and HPLC-DAD analysis using chemically synthesized t-RES conjugate standards. In addition, the amount of t-RES metabolites bound noncovalently to plasma proteins was determined for the first time in humans. The metabolites identified and quantified were t-RES-3-sulfate, t-RES-3,4'-disulfate, t-RES-3,5-disulfate, t-RES-3-glucuronide and t-RES-4'-glucuronide, with t-RES-sulfates being the dominant conjugates in plasma and urine. Besides these metabolites, two novel t-RES-C/O-conjugated diglucuronides have been identified and quantified in plasma and urine. Moreover, it could be shown that up to 50% of the plasma t-RES-3-sulfate, t-RES-disulfates, and the novel t-RES-C/O-diglucuronides were bound to proteins. Total recovery of the dietary administered piceid in urine ranged between 13.6 and 35.7%.
Burkon
Alexander
A
Deutsche Forschungsanstalt für Lebensmittelchemie, Garching, Germany.
Somoza
Veronika
V
D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000378:metabolism / Q000652:urine; D001798:Blood Proteins / Q000378:metabolism; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D020719:Glucuronides / Q000097:blood / Q000378:metabolism* / Q000652:urine; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D012016:Reference Values; D000077185:Resveratrol; D013267:Stilbenes / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine
D000972:Antineoplastic Agents, Phytogenic; D001798:Blood Proteins; D020719:Glucuronides; D013267:Stilbenes; D000077185:Resveratrol