A large number of studies confirmed antihypertensive effect of quercetin. However, due to its low bioavailability, the mechanism of action has been remaining vague and is not likely associated with its antioxidant effect. This study was designed to determinate if quercetin metabolites might be responsible for the activity. During the in vitro study, the vasorelaxant potency of different quercetin metabolites including small phenolic acids formed by bacterial microflora was tested. Metabolites at concentration 10(-7) to 10(-3) M were tested for relaxation of rat thoracic aorta rings precontracted by phenylephrine. Subsequently the most active structure was selected for in vivo experiments, when the effect on blood pressure and heart rate was monitored after i.v. administration in dose range from 0,2mg/kg to 25mg/kg. The most active structure, 3-(3-hydroxyphenyl)propionic acid, initiated vasorelaxation in concentration of 100nM while quercetin at 500nM. The major quercetin metabolite formed by human enzymes, 3-glucuronide, was almost inactive. During the in vivo study the 3-(3-hydroxyphenyl)propionic acid decreased systolic blood pressure even at dose of 1mg/kg without having an effect on heart rate at this dose. In conclusion, some of quercetin metabolites may have be partly responsible for vasorelaxant activity of orally administered quercetin.
Copyright © 2014. Published by Elsevier Inc.