Efeito ansiolítico da agarana sulfatada da alga marinha Gracilaria cornea em camundongos: estudo neurocomportamental e neuroquímico

Abstract

Sulphated polysaccharides are found in several marine organisms and are of great interest in the medical sciences due to their biological properties, such as: immunomodulatory, antiinflammatory and antitumor capacity. Recently, a sulfated polysaccharide of the agarane type, previously characterized by nuclear magnetic resonance, obtained from the marine macroalgae Gracilaria cornea, has demonstrated antinociceptive effect with central and peripheral action, anti-inflammatory effect and absence of toxicity in vivo. Diseases related to central nervous system (CNS) disorders, especially anxiety and depression, affect thousands of people worldwide, especially in the elderly population. However, affective neurological disorders still lack pharmacological strategies considered effective for symptomatic treatment free of adverse effects. In view of the above, the present study aims to evaluate the anxiolytic effect and the mechanism of biochemical action involved in the CNS of Agarana Sulfatada (AS-Gc) obtained from the red sea kelp Gracilaria cornea, in order to contribute to the search for a better therapeutic alternative for these diseases. Initially, total sulfated polysaccharides (PST) were extracted by enzymatic digestion with papain in 0.1 M sodium acetate buffer, pH 5.0. Then the PST were fractionated by ion exchange chromatography on a DEAE-cellulose column and fraction II was used to evaluate the neurobehavioral activities, through behavioral analysis in experimental models of mice (high cross-maze (LCE), open field , Perforated plaque, rotated rod), and biochemical analysis of cerebral areas (prefrontal cortex (PF) and hippocampus (HP)). For the experiments, Swiss mice, weighing 25-32g, were used, from the breeding stock of the Federal University of Ceará. Animals were treated acutely with AS-Gc at 0.1, 1 or 10 mg / kg intraperitoneally. Thirty minute after treatment, the animals were submitted to behavioral tests. The animals were then euthanized and dissected and the PF and HP brain areas removed for the amino acid analyzes Glutamate (GLU) and gamma-aminobutyric acid (GABA). The results showed that AS-Gc at the dose of 10 mg / kg presented an anxiolytic effect in the LCE and perforated plate models, since it increased all the parameters analyzed in the LCE, as well as the number of holes in the holes of the perforated plate. This effect is probably related to the GABAergic system, since flumazenil, GABAA/Benzodiazepine receptor antagonists, reversed the anxiolytic effect in the two tests evaluated. In the open field test the dose of 10 mg / kg increased the number of quadrants and in the test of rotating rod there was no change. In the biochemical analysis of amino acid concentrations in PFC and hippocampus, SA-Gc did not increase GLU and GABA. In conclusion, our results suggest that the acute treatment with SA-Gc at a dose of 10 mg/kg presented an anxiolytic effect being reversed by the use of flumazenil, suggesting that it is related to the mechanism of GABAergic action. Biochemical analysis confirmed this action by increasing GABA, a potent inhibitory amino acid present in the CNS, in PFC and HC. In addition, in contrast to diazepam, SA-Gc (10mg/kg) had no sedative effect or myorelaxing properties and altered locomotor activity.