Vasorelaxant effect of the dichloromethane fraction from Lippia thymoides involves voltage-gated potassium channels and
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Vasorelaxant effect of the dichloromethane fraction from Lippia thymoides involves voltage-gated potassium channels and the suppression of intracellular calcium in rat aortae Gabriela Olinda de Paiva 1 & Mariana Coelho Brito 1 & Pedro Modesto Nascimento Menezes 1 & Luciano Augusto de Araújo Ribeiro 1 & Fernanda Pires Rodrigues de Almeida Ribeiro 1 & Emanuella Chiara Valença Pereira 2 & Larissa Araújo Rolim 2 & Angélica Maria Lucchese 3 & Fabrício Souza Silva 1 Received: 2 April 2020 / Accepted: 20 August 2020 # Sociedade Brasileira de Farmacognosia 2020
Abstract The crude extract and fractions from the leaves and stems of Lippia thymoides Mart. & Schauer, Verbenaceae, were evaluated to determine their vasorelaxant activity on isolated rat aortae. The chromatographic profile from the crude extract and the most potent fraction was determined by HPLC-DAD. The dichloromethane fraction (LtSD) displayed the more potent vasorelaxant effect on phenylephrine-induced tonic contractions in isolated rat aortae with (EC50 = 38.5 (26.3–56.5) μg/ml) or without (EC50 = 37.9 (28.5–50.5) μg/ml) functional endothelium. LtSD-mediated vasorelaxation in endothelium-intact aortic rings was not altered in the presence of atropine, L-NAME, indomethacin, or methylene blue. Preincubation of endothelium-denuded aortic rings with CsCl, glibenclamide, or tetraethylammonium did not alter the effects of LtSD-induced relaxation, but in the presence of 4-aminopyridine, the concentration-response curve of LtSD (EC50 = 37.63 (32.88–43.06) μg/ml in the absence of blocker) shifted to the right and the EC50 value was significantly increased to 156.0 (129.5–187.8) μg/ml. In addition, preincubation with LtSD plus nifedipine inhibited phenylephrine contractions similarly to LtSD alone. These results indicated that the vasorelaxant mechanisms of LtSD were mediated via endothelium-independent pathways, probably involving the activation of KV channels and the reduction of Ca2+ influx through intracellular stores. Keywords Nitric oxide . Vasorelaxant . Rat aorta . Potassium channels . Intracellular calcium
Introduction Lippia species are widely distributed in Brazil, including approximately 150 species mainly present in the Cerrado vegeElectronic supplementary material The online version of this article (https://doi.org/10.1007/s43450-020-00088-4) contains supplementary material, which is available to authorized users. * Fabrício Souza Silva [email protected] 1
Laboratório de Farmacologia Experimental, Colegiado de Farmácia, Universidade Federal do Vale do São Francisco, Petrolina, PE, Brazil
2
Central de Análises de Fármacos, Medicamentos e Alimentos, Universidade Federal do Vale do São Francisco, Petrolina, PE, Brazil
3
Laboratório de Química de Produtos Naturais e Sintéticos Bioativos, Universidade Estadual de Feira de Santana, Feira de Santana, BA, Brazil
tation or tropical savanna ecoregion of Brazil and rocky fields, some of which are prevalent in the Caatinga biome (Simões et al. 2015). In Northeastern Brazi
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