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Vascular deconjugation of quercetin glucuronide: The flavonoid paradox revealed?

Authors

  • Carmen Menendez,

    1. Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
    2. Ciber Enfermedades Respiratorias (CIBERES), Bunyola, Spain
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    • These authors contributed equally to this work.

  • Montserrat Dueñas,

    1. Grupo de Investigación en Polifenoles (GIP-USAL), Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain
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    • These authors contributed equally to this work.

  • Pilar Galindo,

    1. Department of Pharmacology, School of Pharmacy, Universidad de Granada, Granada, Spain
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  • Susana González-Manzano,

    1. Grupo de Investigación en Polifenoles (GIP-USAL), Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain
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  • Rosario Jimenez,

    1. Department of Pharmacology, School of Pharmacy, Universidad de Granada, Granada, Spain
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  • Laura Moreno,

    1. Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
    2. Ciber Enfermedades Respiratorias (CIBERES), Bunyola, Spain
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  • Maria José Zarzuelo,

    1. Department of Pharmacology, School of Pharmacy, Universidad de Granada, Granada, Spain
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  • Isabel Rodríguez-Gómez,

    1. Department of Physiology, School of Medicine, Universidad de Granada, Granada, Spain
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  • Juan Duarte,

    1. Department of Pharmacology, School of Pharmacy, Universidad de Granada, Granada, Spain
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  • Celestino Santos-Buelga,

    1. Grupo de Investigación en Polifenoles (GIP-USAL), Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain
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  • Francisco Perez-Vizcaino

    Corresponding author
    1. Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
    2. Ciber Enfermedades Respiratorias (CIBERES), Bunyola, Spain
    • Department of Pharmacology, School of Medicine, Universidad Complutense, 28040 Madrid, Spain Fax: +34-913941465
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Abstract

Scope: 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.

Methods and 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.

Conclusion: We propose that Q3GA behaves as a quercetin carrier in plasma, which deconjugates in situ releasing the aglycone which is the final effector.

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