Efeitos comportamentais, neuroquímicos e antioxidante da hecogenina obtida de Agave sisalana Perrine em Camundongos

Abstract

Agave sisalana, popularly known as sisal, is a plant originaly from Mexico and belongs to the family Agavaceae. Hecogenin (HEC) is a steroidal sapogenin found in the juice from the leaves of Agave. The purpose was to study the behavioral, neurochemical and antioxidant effects of HEC in mice. We used swiss mice weighing 25-35 g. The behavioral effects of HEC‟s acute administration (5, 10, 20, or 40 mg/kg intraperitoneally – i.p.) or in repeated doses for seven days (20 or 40 mg/kg, i.p.), were evaluated by tests: elevated plus maze, open field, hole board test and tail suspension. In these tests, we determined the mechanism of action of HEC with acute administration of Flumazenil 2.5 mg/kg (FLU) or Reserpine 2 mg/kg (RES). After the behavioral tests, the brain areas pre-frontal cortex (PFC), hippocampus (HC) and striatum (CE) were dissected. The elevated plus-maze test showed that HEC, acutely administered, at doses of 10, 20 or 40 mg/kg, caused a significant increase in the number of entries in the open arms (NEOA) compared to control. A similar effect was observed in the time spent in the open arms (TPOA) at doses of 20 or 40 mg/ kg compared to the control group. The administering repeated doses of HEC (20 or 40 mg/kg) increased the NEOA. HEC (20 or 40 mg/kg) administered acutely increased the number of head dips compared to control. A similar effect was observed after treatment with repeated doses of HEC at a dose of 40 mg/kg compared to the control group. The FLU was unable to reverse the acute anxiolytic effects of HEC in the elevated plus-maze test and in the hole board test. Hecogenin reduced the immobility time in the tail suspension test after acute treatment or repeated doses. The molecule under study (HEC) reversed the depressant effect of RES. Related to the effects of acute administration of HEC on lipid peroxidation, we observed a decrease in the three studied areas at 5, 10, 20 or 40 mg/kg doses, compared to control groups. At doses of 20 or 40 mg/kg, HEC caused decreased levels of nitrite in the PFC, HC and CE compared to control. In PFC‟s mice acutely treated with HEC, the excitatory amino acid glutamate (GLU) increased at doses of 10, 20 or 40mg/kg, while the inhibitory gamaaminobutiric acid (GABA) and taurine (TAU) increased at doses of 20 or 40mg/kg. In the mice‟s hippocampus treated with HEC, there was increased aspartate (ASP), GLU, glycine (GLY) and TAU only at the highest dose HEC. In the striatum, there was an increase of ASP, and GLU and TAU after doses of 20 or 40 mg/kg of HEC. Concentrations of GLY and GABA increased HEC at the highest dose (40 mg/kg) in this brain area. The 5-HT and 5-HIAA levels were increased only in 40 mg/kg dose of HEC. We concluded that HEC (20 or 40 mg/kg) showed anxiolytic effects and this effect was not related to benzodiazepine receptors. The molecule did not cause oxidative stress to the CNS.