Efeito tipo antidepressivo e ansiolítico do extrato etanólico de egletes viscosa e de seu metabólito Conizaleucolideo A: envolvimento de mecanismos monoaminérgicos, antioxidantes e anti-inflamatórios

Abstract

The Egletes viscosa specie, from Asteraceae family, is a common wild grass in the wilderness and the northeastern coast of Brazil, popularly known as true macela. The plant has as main uses digestive and intestinal problems, cramps, gas , heartburn, indigestion, diarrhea and headache. Previous studies have led to relate possible central effects of this plant species. Aiming to search for better therapeutic alternatives for treatment of depression and anxiety in humans, it evaluated its possible central effects in preclinical models of mice. Classic models were used in screening for sedative / hypnotic and antidepressant agents, such as the open field (CA), rota rod (RR), plus maze (LCE), forced swimming test (TNF) and suppression of sucrose (SC). For the study, we used the ethanolic extract at doses of 100 and 200 mg / kg, besides the isolated major constituent of this extract, a diterpene furan called colizaleucolídeo A, at doses of 25 and 50 mg / kg. It has been shown that drugs presented anxiolytic and antidepressant activity. A target site to the related anxiolytic effects is the GABA receptor, which was shown in the plus maze test with the GABA antagonist flumazenil. Following, evaluation tests of antidepressant effect with two behavioral models were performed, the forced swimming test (TNF) and the suppression of sucrose (SC), having de LPS (lipopolysaccharide) intraperitoneal as the inductor of similar to depression behaviour. Through these models, it was observed an antidepressant effect not related to psychostimulant actions, and that seems to be mediated, at least in part by an interaction with the dopaminergic system (D1 and D2 receptors), noradrenergic (receptor α1) and serotonin (receptor 5-HT1A). It was also analyzed the anti-inflammatory and antioxidant effects, known to be related to the pathophysiology of depression. Using lipopolysaccharide as an inducer of the depressive state, it changed the nitrite levels, reactive thiobarbituric acid (TBARS), the enzyme myeloperoxidase (MPO ) as well as reduced the levels of reduced glutathione (GSH), all the effects consistent with the depressive state. The performance of the materials extracted from E. viscosa was found in the prevention and reversal of changes in the prefrontal cortex, hippocampus and nucleus of base, where it could reverse the effects of lipopolysaccharide in the studied parameters. Imipramine was used as a standard drug both in prevention and in reversing the depressive state in animals. The data suggest the use of E. viscosa ethanol extract and the diterpene colizaleucolídeo A as antidepressant.