title: Vascular deconjugation of quercetin glucuronide: the flavonoid paradox revealed?
abstract: METHODS
  The dietary flavonoid quercetin exerts protective cardiovascular effects. Because quercetin is rapidly metabolized into less active or inactive glucuronidated metabolites and the plasma concentrations of free quercetin are very low, a huge amount of scientific data generated along decades with the unconjugated compounds in vitro has been questioned. We aimed to determine whether glucuronidated quercetin can deconjugate in situ and whether deconjugation leads to a biological effect.
  
  
  RESULTS
  Quercetin and quercetin-3-O-glucuronide (Q3GA) were perfused through the isolated rat mesenteric vascular bed. Quercetin was rapidly metabolized in the mesentery. In contrast, the decay of Q3GA was slower and was accompanied by a progressive increase of quercetin in the perfusate and in the tissue over 6 h, which was prevented by the β-glucuronidase inhibitor saccharolactone. Incubation of mesenteric arterial rings mounted in a wire myograph with Q3GA for ≥1 h resulted in a significant inhibition of the contractile response which was also prevented by saccharolactone. Moreover, the intravenous administration of Q3GA resulted in a slow onset and sustained blood pressure lowering effect, demonstrating for the first time that Q3GA has effects in vivo.
  
  
  CONCLUSIONS
  We propose that Q3GA behaves as a quercetin carrier in plasma, which deconjugates in situ releasing the aglycone which is the final effector.
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Menendez
authors.forename: Montserrat
authors.initials: M
authors.lastname: Dueñas
authors.forename: Pilar
authors.initials: P
authors.lastname: Galindo
authors.forename: Susana
authors.initials: S
authors.lastname: González-Manzano
authors.forename: Rosario
authors.initials: R
authors.lastname: Jimenez
authors.forename: Laura
authors.initials: L
authors.lastname: Moreno
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Zarzuelo
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodríguez-Gómez
authors.forename: Juan
authors.initials: J
authors.lastname: Duarte
authors.forename: Celestino
authors.initials: C
authors.lastname: Santos-Buelga
authors.forename: Francisco
authors.initials: F
authors.lastname: Perez-Vizcaino
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D005937:Glucaric Acid / Q000031:analogs & derivatives / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D011794:Quercetin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D051381:Rats
chemical_list: D002317:Cardiovascular Agents; D006023:Glycoproteins; C011473:beta-glucuronidase inhibitor; C443401:quercetin 3-O-glucuronide; C009194:saccharolactone; D011794:Quercetin; D005966:Glucuronidase; D005937:Glucaric Acid