title: Gastrointestinal absorption and metabolism of hesperetin-7-O-rutinoside and hesperetin-7-O-glucoside in healthy humans.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Nestlé Research Center, Nestec Ltd, Lausanne, Switzerland.
authors.forename: Lucas
authors.initials: L
authors.lastname: Actis-Goretta
authors.affiliation: Faculty of Life Sciences, Bradford School of Pharmacy, University of Bradford, Bradford, UK.
authors.forename: Tristan P
authors.initials: TP
authors.lastname: Dew
authors.affiliation: Nestlé Research Center, Nestec Ltd, Lausanne, Switzerland.
authors.forename: Antoine
authors.initials: A
authors.lastname: Lévèques
authors.affiliation: Department of Technology, Postharvest and Food Industry, IFAPA-Alameda del Obispo, Córdoba, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Pereira-Caro
authors.affiliation: Nestlé Research Center, Nestec Ltd, Lausanne, Switzerland.
authors.forename: Maarit
authors.initials: M
authors.lastname: Rein
authors.affiliation: Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Teml
authors.affiliation: Department of Gastroenterology and Hepatology, Robert Bosch Hospital, Stuttgart, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schäfer
authors.affiliation: Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Hofmann
authors.affiliation: Department of Clinical Pharmacology, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.affiliation: Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Eichelbaum
authors.affiliation: Department of Nutrition, University of California, Davis, CA, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Crozier
authors.affiliation: School of Food Science and Nutrition, University of Leeds, Leeds, UK.
authors.forename: Gary
authors.initials: G
authors.lastname: Williamson
mesh_terms: D000328:Adult; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D018592:Cross-Over Studies; D005260:Female; D065569:Gastrointestinal Absorption; D064368:Healthy Volunteers; D006569:Hesperidin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D008297:Male; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: C545247:hesperetin-7-glucoside; D006569:Hesperidin
keywords: Absorption; Hesperetin glycosides; Humans; Metabolism; Oral intake; Perfusion of proximal jejunum