Cardiovascular protection by flavonoids. Pharmacokinetic mystery
DOI:
https://doi.org/10.4321/s2340-98942015000400002Keywords:
Quercetin, Hypertension, Plasma MetabolitesAbstract
Objetives. Flavonoids have been proposed to exert beneficial effects in the prevention of cardiovascular diseases. In this review we try to clarify some fundamental questions regarding efficacy, mechanism of action and bioavailability of one of the most widely distributed flavonoids in the diet, quercetin.
Methods. The database of the National Library of Medicine, Washington, DC (MEDLINE PubMed) was used and all the studies in animals and humans available from inception of the database until November 2015 were collected.
Results. Quercetin exerts vasodilatory and antihypertensive effects in animal models of hypertension and hypertensive subjets. Quercetin is effective in all models of hypertension analyzed, independently of the origin of the hypertension, the status of renin–angiotensin system, oxidative stress, nitric oxide, and other factors. Paradoxically, despite exerting biologically demonstrable systemic effects, it is not found in plasma after oral administration and its circulating metabolites show weak activity in vitro. Quercetin is extensively metabolized into methylated and glucurono- and sulfo-conjugated metabolites, which are the plasma circulating forms; and glucurono-, but not sulfo-conjugates, can be hydrolyzed at the vascular level, yielding the parent aglycone which accumulates in tissues. Thus conjugation is a reversible process and, at least regarding the vasodilator and antihypertensive effects, the conjugation-deconjugation cycle appears to be an absolute requirement.
Conclusions. Glucuronidated derivatives transport quercetin and its methylated form, and deliver to the tissues the free aglycone, which is the final effector.
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