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|Title:||Gastrointestinal absorption and metabolism of hesperetin-7-O-rutinoside and hesperetin-7-O-glucoside in healthy humans|
|Citation:||Molecular Nutrition and Food Research, 2015; 59(9):1651-1662|
|Lucas Actis-Goretta, Tristan P. Dew, Antoine Lévèques, Gema Pereira-Caro, Maarit Rein, Alexander Teml, Christian Schäfer, Ute Hofmann, Matthias Schwab, Michel Eichelbaum, Alan Crozier and Gary Williamson|
|Abstract:||Scope: Hesperetin-7-O-rutinoside (hesperidin) reduces blood pressure in healthy volunteers but its intestinal absorption and metabolism are not fully understood. Therefore, we aimed to determine sites of absorption and metabolism of dietary flavanone glycosides in humans. Methods and Results: Using a single-blind, randomized crossover design, we perfused equimolar amounts of hesperetin-7-O-rutinoside and hesperetin-7-O-glucoside directly into the proximal jejunum of healthy volunteers. We assessed the appearance of metabolites in the perfusate, blood and urine, to determine the sites of metabolism and excretion, and compared this to oral administration. The glucoside was rapidly hydrolyzed by brush border enzymes without any contribution from pancreatic, stomach, or other secreted enzymes, or from bacterial enzymes. Only ∼3% of the dose was recovered intact in the perfusate, indicating high absorption. A proportion was effluxed directly back into the perfused segment mainly in the form of hesperetin-3'-O-sulfate. In contrast, very little hydrolysis or absorption of hesperetin-7-O-rutinoside was observed with ∼80% recovered in the perfusate, no hesperetin metabolites were detected in blood and only traces were excreted in urine. Conclusion: The data elucidate the pathways of metabolism of dietary hesperidin in vivo and will facilitate better design of mechanistic studies both in vivo and in vitro.|
|Keywords:||Absorption; hesperetin glycosides; humans; metabolism; oral intake; perfusion of proximal jejunum|
|Rights:||© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim|
|Appears in Collections:||Medicine publications|
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