Background:

Ayanin (3,7,4'-Tri-O-methylquercetin) and 3,7-Di-O-methylquercetin (DMQ) are the main active metabolites isolated by bioguided fractionation from Croton schiedeanus, species known popularly in Colombia as “almizclillo”, which has been studied in experimental models in rats, exerting vasodilator and antihypertensive effects. Also, when the effect of these flavonoids was studied separately, important vasodilation was observed.

Objective:

To evaluate whether flavonoids from Croton schiedeanus have synergistic vasodilator properties when different combinations are used in isolated aorta rings.

Methods:

Cumulative concentrations of ayanin (10-8 M - 6x10-5 M or 0.01 µM - 60 µM) were assayed in the absence and presence of an increasing concentration of 3,7-Di-O-methylquercetin (DMQ) (10-8 - 3x10-5 M or 0.01-30 µM) in isolated rings from Wistar rats, pre-contracted with phenylephrine. The concentration-response curve with the maximal effect was compared with that obtained by Croton schiedeanus whole ethanolic extract (10-6 - 3x10-4 g/mL). Also, this combination was assayed in the presence of the nitric oxide synthetase inhibitor L-NAME (10-4 M) and the guanylate cyclase inhibitor methylene blue (10-4 M) to assess the role of the NO/cGMP pathway in this interaction.

Results:

Ayanin and DMQ display a dual interaction in vascular relaxant response: agonism at higher concentration ranges (10-6 - 3x10-5 M or 1-30 µM), and antagonism at lower concentration ranges (10-8 - 3x10-7 M or 0.01-0.3 µM). The efficacy at the highest concentration was greater than that obtained by the whole extract (Emax: 98.4% vs. 33.9%). This response was decreased but not reverted in the presence of L-NAME and methylene blue. Thus, the vasodilator effect of this combination does not depend entirely on the NO/cGMP cyclic pathway.

Conclusion:

The combined use of appropriate concentrations of these flavonoids could represent an advantage over Croton schiedeanus whole extract for vasodilator purposes.

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