Atividade espasmolítica do extrato metanólico bruto obtido das partes aéreas de Evolvulus linarioides Meisn. (Convolvulaceae) e seu possível mecanismo de ação em íleo isolado de cobaia

• Ano de defesa: 2020
• Autor(a) principal: Silva, Gleice Rayanne da
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal da Paraíba; Brasil; Farmacologia; Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos; UFPB
• Palavras-chave em Português: Evolvulus linarioides; Atividade espasmolítica; Canais de cálcio; Mobilização de cálcio; Íleo de cobaia; Spasmolytic activity; Calcium channels; Calcium mobilization; Guinea-pig ileum; CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
• Link de acesso: https://repositorio.ufpb.br/jspui/handle/123456789/18667

Several species of Convolvulaceae are popularly used to treat smooth muscle disorders and others have already shown spasmolytic effect. Among the species of this family, Evolvulus linarioides Meisn., stands out, a species commonly found in the states of Bahia, Minas Gerais, Pernambuco and Paraíba. Thus, this study aimed to investigate the spasmolytic activity of the crude methanolic extract obtained from the aerial parts (EL-MeOHAP) in rat aorta and trachea, rat uterus and guinea-pig ileum, in addition to characterizing its mechanism of action in the organ it presented greater relaxing power. All functional experimental protocols (n = 5) performed were approved by the UFPB Ethics Committee on the Use of Animals (certificate 3059100918). EL-MeOHAP showed non-selective spasmolytic activity in the tested organs, being more potent in rat trachea (EC50 = 139.4 ± 17.4 μg/mL) and guinea-pig ileum (IC50 = 124.8 ± 18.1 μg/mL). Following the study of the mechanism of action in guinea-pig ileum, it was observed that EL-MeOHAP relaxed the ileum pre-contracted with KCl 40 mM (EC50 = 53.5 ± 5.7 μg/mL), carbachol 10-6 M (EC50 = 49.6 ± 7.2 μg/mL) or histamine 10-6 M (EC50 = 36.0 ± 5.2 μg/mL) in an equipotent manner, suggesting that the extract should inhibit the Ca2+ influx through voltage-dependent Ca2+ channels (Cav). This hypothesis was confirmed, since the extract inhibited the cumulative contractions induced by CaCl2 in depolarizing medium (70 mM KCl) nominally without calcium. In addition, EL-MeOHAP relaxed the ileum pre-contracted with S-(-)-Bay K8644, a Cav1 agonist (EC50 = 83.2 ± 6.4 μg/mL), compared to the effect observed with KCl, demonstrating that the extract directly inhibits the influx of Ca2+ through Cav1. Other relaxation pathways were also investigated, however it was found that K+ channels, adrenergic, nitric oxide and cyclooxygenase pathway were not involved in the spasmolytic effect of this extract in guinea-pig ileum. Knowing that the mechanisms of Ca2+ mobilization in muscle cells of the circular and longitudinal layers are different, a possible blockage of Ca2+ mobilization from intracellular stores was also investigated. Therefore, the circular layer of guinea-pig ileum was used, and it was observed that the extract antagonized the phasic contractions induced by histamine 10-5 M (EC50 = 53.5 ± 5.7 μg/mL), thus modulating negatively the release of Ca2+ from intracellular stores. In view of this, it was possible to infer that EL-MeOHAP has non-selective activity in the tested organs and that its mechanism of action in isolated guinea-pig ileum involves blocking the Ca2+ influx by Cav1, in addition to a negative modulation of Ca2+ release mechanisms from intracellular stores, resulting in a reduction in [Ca2+]c, thus promoting muscle relaxation.