Virtual Conference
Pharma Conference 2022

Alejandra Paola Ortiz Sánchez

Universidad Nacional de Colombia, Colombia

Title: Vascular interactions of the main flavonoid metabolites isolated from Croton schiedeanus “Almizclillo”


Combination therapy is an effective therapeutic strategy in clinical practice when the agents improve the pharmacological response, allow to reduce the doses and the risk of potential adverse effects1. With this therapeutic approach, new therapeutic alternatives are researched to reduce the current notable impact of arterial hypertension on public health. Natural sources as Croton schiedeanus could provide the active principles 3,7,4’-Tri-O-methylquercetin or ayanin and 3,7-Di-O-methylquercetin or DMQ, which could interact in a synergistic way and offer new pharmacological options of combination therapy2 3. Cumulative concentrations of ayanin (10-8 M - 6x10-5 M) were assayed in the absence and presence of an increasing concentration of DMQ (10-8 – 3x10-5 M) in isolated rings from Wistar rats, pre-contracted with phenylephrine. The concentration-response curve with the maximal effect was compared with that obtained by C. 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 interaction4. Results were treated in GraphPad and Combenefit. Results showed that Ayanin and DMQ display a dual interaction in vascular relaxant response: agonism at higher concentration ranges (10-6 – 3x10-5 M) and antagonism at lower concentration ranges (10-8 – 3x10-7 M).

The efficacy at the highest concentration was greater than that obtained from 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 5. Thus, the vasodilator effect of this combination does not depend entirely on the NO/cGMP cyclic pathway. Finally, 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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