ABSTRACT
Aims: South Brazilian Hypericum species are a source of dimeric structures, constituted of filicinic acid and phloroglucinol moieties, which present antidepressant-like effects mediated by monoaminergic neurotransmission in rodents. Here, we show that hyperbrasilol B, a phloroglucinol derivative from Hypericum caprifoliatum, presents antidepressant-like activity in mice forced swimming test (FST). The aim of this study was to determinate if Na+ channels are important to the antidepressant-like effect of hyperbrasilol B and also verify the effect of this compound on Na+, K+ ATPase activity in the cerebral cortex and hippocampus of mice. Methodology: We assessed the effects of veratrine, a Na+ channel opener on antidepressant-like effect of hyperbrasilol B by using mice FST. Veratrine (0.06 mg/kg) and hyperbrasilol B (10 mg/kg) were given i.p. 60 and p.o. 30 min, respectively, before the test. In another batch of experiments different groups of mice were treated with hyperbrasilol B 10 mg/kg, p.o. (Single administration or once a day during 3 days). Two hours after the acute or after the last of the three treatments, the brain structures were removed for measuring Na+, K+ ATPase activity. Results: Veratrine was able to prevent the anti-immobility effect of hyperbrasilol B on the FST, suggesting that its antidepressant-like effect might be due to Na+ influx modifying properties. Animals treated for 3 consecutive days with hyperbrasilol B presented a significant increase in the hippocampus Na+, K+ ATPase activity. The acute treatment was ineffective. Conclusion: Alterations in the Na+ gradient may be implicated in the antidepressant-like effect of hyperbrasilol B.
ABSTRACT
Na última década, o gênero Hypericum ganhou repercussão mundial devido à utilização de Hypericum perforatum para obtenção de medicamentos antidepressivos. Por esta razão, a maioria dos estudos com outras espécies do gênero centra-se nesta atividade. Porém, um dos usos populares de espécies de Hypericum nativas do sul do Brasil é no tratamento de problemas gastrintestinais, inclusive como antiespasmódico. Neste trabalho, foi avaliado o efeito de uma das espécies de Hypericum nativas do Rio Grande do Sul, H. caprifoliatum, sobre as contrações induzidas por agonistas em íleo isolado de cobaio. Foi investigado o efeito de um extrato ciclo-hexano purificado (isento de clorofila e ceras), nas concentrações de 1, 3, 10 e 30 mg/mL, sobre curvas cumulativas de acetilcolina, histamina, potássio e serotonina (10-7 a 10-4 M). Na concentração de 30 mg/mL o extrato inibiu totalmente as contrações induzidas por todos os agonistas. Na concentração de 10 mg/mL, o extrato apresentou efeito antagonista não-competitivo de serotonina, reduzindo a contração máxima induzida por serotonina em cerca de 50 por cento. A resposta contrátil aos outros mediadores não foi alterada. Estes resultados indicam que espécies de Hypericum do sul do Brasil podem ser uma perspectiva interessante na busca de moléculas com atividade sobre a motilidade gastrintestinal.
In the last decade the genus Hypericum has achieved worldwide recognition due to the therapeutic value of H. perforatum as an antidepressant drug. Consequently this activity is the most investigated one. However, species native to Brazil have other folk uses such as for the treatment of digestive disorders, including cramps. In this study we evaluated the effect of a purified cyclohexane extract (chlorophyll and waxes free) (1,3,10 and 30 mg/mL) of H. caprifoliatum, a specie native to South Brazil, on isolated guinea pig ileum contractions induced by different mediators: serotonin, histamine, acetylcholine and potassium chloride (10-7 - 10-4 M). At 30 mg/mL all contractile responses were abolished. At 10 mg/mL only serotonin responses were altered: the extract reduced the maximal effect in 50 percent, which represents a non-competitive antagonism. At 1 and 3 mg/mL the extract was unable to modify all mediators response. These results point to native species of Hypericum as an interesting perspective in searching new molecules active on gastrointestinal motility.