The Antidepressant-like Effect of Hyperbrasilol B, A Natural Dimeric Phloroglucinol Derivative is Prevented by Veratrine, a Sensitive-Voltage Na+ Channel Opener
Fernanda Bossemeyer Centurião
Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande of Sul, Porto Alegre, Brazil
Satchie Sakamoto
Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande of Sul, Porto Alegre, Brazil
Ana Cristina Stein
Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande of Sul, Porto Alegre, Brazil
Liz Girard Müller
Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande of Sul, Porto Alegre, Brazil
Pietro Maria Chagas
Department of Chemistry, Natural and Exact Sciences Center, Federal Univeristy of Santa Maria, Santa Maria, Brazil
Gilsane Von Poser
Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande of Sul, Porto Alegre, Brazil
Cristina Wayne Nogueira
Department of Chemistry, Natural and Exact Sciences Center, Federal Univeristy of Santa Maria, Santa Maria, Brazil
Stela Maris Kuze Rates *
Pharmaceutical Sciences Graduate Program, Federal University of Rio Grande of Sul, Porto Alegre, Brazil
*Author to whom correspondence should be addressed.
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.
Keywords: Hypericum caprifoliatum, phloroglucinol derivatives, depression, hyperbrasilol B, Na channels, 1 12