title: The flavonoid quercetin induces acute vasodilator effects in healthy volunteers: correlation with beta-glucuronidase activity.
abstract: Quercetin exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in hypertensive humans and animal models. We hypothesized that oral quercetin might induce vasodilator effects in humans and that they might be related to the deconjugation of quercetin-3-O-glucuronide (Q3GA).
  
  
  METHODS
  double blind, randomized, placebo-controlled trial. Fifteen healthy volunteers (26±5 years, 6 female) were given a capsule containing placebo, 200 or 400mg of quercetin in random order in three consecutive weeks. At 2h a dose-dependent increase in Q3GA was observed in plasma (∼0.4 and 1μM for 200 and 400mg, respectively) with minor levels of quercetin and isorhamnetin. No changes were observed in blood pressure. At 5h quercetin induced and increase in brachial arterial diameter that correlated with the product of the levels of Q3GA by the plasma glucuronidase activity. There was an increase in urinary levels of glutathione but there was no increase in nitrites plus nitrates. Quercetin and isorhamnetin also relaxed human umbilical arteries in vitro while Q3GA was without effect. In conclusions, quercetin exerts acute vasodilator effects in vivo in normotensive, normocholesterolemic human subjects. These results are consistent with the effects being due to the deconjugation of the metabolite Q3GA.
authors: Servicio de Nefrologia, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors: Almudena
authors: A
authors: Perez
authors: Grupo de Investigacion en Polifenoles (GIP-USAL), Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.
authors: Susana
authors: S
authors: Gonzalez-Manzano
authors: Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain; Instituto de Investigación Biosanitaria de Granada, Spain.
authors: Rosario
authors: R
authors: Jimenez
authors: Servicio de Nefrologia, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors: Rocío
authors: R
authors: Perez-Abud
authors: Service of Gynecology, Clinic Hospital of Granada, Granada, Spain.
authors: Jose M
authors: JM
authors: Haro
authors: Servicio de Nefrologia, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors: Antonio
authors: A
authors: Osuna
authors: Grupo de Investigacion en Polifenoles (GIP-USAL), Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.
authors: Celestino
authors: C
authors: Santos-Buelga
authors: Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain; Instituto de Investigación Biosanitaria de Granada, Spain.
authors: Juan
authors: J
authors: Duarte
authors: Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; Ciber Enfermedades Respiratorias (Ciberes), Spain; Instituto de Investigacion Sanitaria Gregorio Marañon (IISGM), Spain. Electronic address: fperez@med.ucm.es.
authors: Francisco
authors: F
authors: Perez-Vizcaino
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005966:Glucuronidase / Q000097:blood* / Q000378:metabolism; D005978:Glutathione / Q000652:urine; D064368:Healthy Volunteers; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D009566:Nitrates / Q000652:urine; D009573:Nitrites / Q000652:urine; D011794:Quercetin / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D014469:Umbilical Arteries / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D009566:Nitrates; D009573:Nitrites; D014665:Vasodilator Agents; C443401:quercetin 3-O-glucuronide; C047368:3-methylquercetin; D011794:Quercetin; D005966:Glucuronidase; D005978:Glutathione
keywords: Glucuronidase; Human; Metabolites; Quercetin; Vasodilation