Investigação da atividade espasmolítica do extrato etanólico bruto das partes aéreas de Hyptis macrostachys Benth. (Lamiaceae) e do seu composto isolado HM308.

Abstract

Hyptis are a worldwide genus cited by their many medicinal uses. Hyptis macrostachys Benth., a species popularly known as “alfavaca-brava” and “hortelã-do-mato”, is used in folk medicine to relief asthma, cough and bronchitis symptoms. From the aerial parts ethanolic extract from H. macrostachys was obtained a pyrone (HM308). Thus, in this work was investigated a possible spasmolytic effect of ethanolic extract of aerial parts from Hyptis macrostachys Benth. (HM-EtOHPA) and its isolated compound, HM308, on smooth muscle models. We observed that on rat uterus, rat aorta and guinea pig trachea HM-EtOHPA showed a significant spasmolytic action, but not in a concentration-dependent manner (Emax = 76.1 ± 5.1%; Emax = 99.1 ± 0.9%; Emax = 43.2 ± 5.8%, respectively), so it is not viable proceed the investigation in these organs. However, on guinea pig ileum HM-EtOHPA (9-729 μg/mL) inhibited significantly and concentration-dependently phasic contractions induced by 10-6 M carbachol (CCh) or histamine (IC50 = 164.7 ± 36.9 and 93.2 ± 22.2 μg/mL, respectively) as well as relaxed this organ in an equipotent, significant and concentration-dependent manner (1-729 μg/mL) when contracted by 10-6 M CCh, 10-6 M histamine or 40 mM KCl suggesting an action in a common step of the signalling pathway of these contractile agents, which could be the voltage-gated calcium channels (CaV) blockade. This was confirmed, since HM-EtOHPA (9-729 μg/mL) inhibited Ca2+-induced contractions in a medium nominally without Ca2+, shifiting the curves to right in a non-parallel manner with Emax reduction and relaxed ileum pre-contracted by 3 x 10-7 M S-(-)-Bay K8644 in a concentrationdependent manner (EC50 = 444.4 ± 159.6 μg/mL). The compound HM308, in a similarly to HM-EtOHPA, in rat uterus HM308 showed a low efficacy. However, were observed that HM308 do not showed relaxant effect in rat aorta and guinea pig trachea. Interestingly, in guinea pig ileum, HM308 (10-5 –3 x 10-4 M) inhibited in a significant and concentration-dependent manner the phasic contractions induced by 10-6 M CCh or 10-6 M histamine (IC50 = 1.7 ± 0.3 x 10-4 and 0.9 ± 0.05 x 10-4 M, respectively), being more potent in antagonize contractions induced by histamine. Thereby, both HM-EtOHPA and the pyrone HM308 showed spasmolytic effect, and the extract action, on guinea pig ileum, probably is due to calcium influx blockade through Cav. However additional mechanism are not discarded in the extract action, as well as other studies are necessary to better characterize the spasmolytic effect of HM308.