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Abstract: The present study evaluated anxiolytic activity of (+)-limonene epoxide (EL), through the marble burying test (MBT) assay, and the antioxidant potential in vitro and in vivo in mice hippocampus of adult mice subjected to experimental anxiety protocol. For behavioral studies, and in vivo antioxidant analyses, mice were treated orally with 0.05% Tween 80 dissolved in 0.9% saline solution (vehicle), ascorbic acid 250mg/kg, diazepam (2mg/kg) and EL (25, 50 and 75mg/kg). Results suggest an anxiolytic effect of (+)-limonene epoxide. A reduction in number of buried marbles in groups treated with EL doses of 25, 50 and 75mg/kg was observed when compared with diazepam and vehicle groups. This reduction was observed after treatments with single and repeated doses, reinforcing the hypothesis of anxiolytic effect. The anxiolytic effect was reversed by pretreatment with flumazenil (25mg/kg, o.r) in the same way as it was observed with diazepam (2mg/kg, o.r, positive control), suggesting that these drugs possess a similar mechanism of action. In antioxidant tests in vitro, the concentrations from 0.9 to 7.2μg/ml were tested. The results of in vitro antioxidant tests demonstrated a 50% inhibitory effective concentration of 0.7342, 1.296 and 1.169μg/ml against the formation of nitrite ion, hydroxyl radical and reactive substances to thiobarbituric acid, respectively. The treatment with EL reduced the lipid peroxidation level and nitrite content, suggesting an antioxidant role in vivo since it was able to reduce the formation of reactive species derived from oxygen and nitrogen. Furthermore, the EL increased activity of enzymes catalase and superoxide dismutase in mice hippocampus, suggesting that their role may be due to antioxidant upregulation of these enzymes. [Copyright &y& Elsevier]

Epileptic syndromes are highly prevalent neurological conditions and can often be disabling. In order to find an alternative for treatment, this study evaluated anticonvulsant effects of carvacryl acetate (CA), a derivative of monoterpene carvacrol, after seizures induced by pilocarpine (P400), picrotoxin (PIC) or pentylenetetrazol (PTZ). We also analyzed the CA effects on Na + , K + -ATPase and δ-aminolevulinic acid dehydratase (δ-ALA-D) activities in hippocampus mice after seizures induced by P400, PIC or PTZ. In addition, glutamate, δ-aminobutyric acid (GABA), glutamine and aspartate levels in mice hippocampus treated with CA after seizures induced by P400, PIC or PTZ were also measured. CA produced anticonvulsant effects against seizures induced by P400, PIC or PTZ, and its effects were reversed by flumazenil, suggesting that action mechanism can be mediated by GABAergic system. CA increased GABA levels, but did not alter glutamate and aspartate concentrations in mice hippocampus after seizures induced by P400, PIC or PTZ when compared with seizures induced by P400, PIC or PTZ ( p < 0.05), respectively, as well as decreased glutamine content in mice hippocampus after seizures induced by PIC when compared with seizures induced by PIC ( p < 0.05). In addition, CA also increased Na + , K + -ATPase and δ-aminolevulinic acid dehydratase activities after seizures induced by P400, PIC or PTZ when compared with seizures induced by P400, PIC or PTZ ( p < 0.05), respectively. This study demonstrated that CA could be a future therapeutic option for treatment of epilepsy, with a multifactorial brain action mechanism. [ABSTRACT FROM AUTHOR]

The essential oil of Myrtus communis L. (Myrtaceae) and its compounds have been popularly used in numerous health disorders, including insomnia and nervous conditions, but their effects on central nervous system (CNS) have not been explored yet. We evaluated the anxiolytic-like effects and possible action mechanism of (−)-myrtenol (MYR), a monoterpenoid alcohol present in essential oil of M. communis L. Animal models of elevated plus maze (EPM), light–dark transition (LDT), open field and rotarod tests were used in the present study. MYR was administered in male rats. Diazepam was used as the standard drug (positive control) and flumazenil was used to elucidate the possible action mechanism. The results showed that none of the doses of MYR had effect on the resistance time in rotating bar, but caused reduction in the number of falls in rotarod tests when compared with a negative control. Similarly, MYR had no effect on the number of crossings, groomings or rearings in open field tests when compared with a negative control. However, in EPM and LDT tests, MYR significantly increased ( p < 0.001) the number of entries in open arms ( F 7,49 = 9.867), the time spent in open arms ( F 7,49 = 53.97) and the time spent in light compartment ( F 7,56 = 27.38), when compared with negative and positive controls, respectively. Flumazenil was able to reverse the effects of diazepam and MYR. These results suggest that MYR presents anxiolytic-like activity and that effect can be mediated by GABAergic transmission. [ABSTRACT FROM AUTHOR]

We have reported Riparin A as a promising antiparasitic molecule ​​against Leishmania amazonensis promastigotes. This work evaluated the acute oral toxicity of Riparin A and its anxiolytic effects using in vivo models and computational tools. Mice were submitted to acute oral toxicity tests (Guideline OECD 423). Later, anxiety assays with Riparin A (50, 100 and 200 mg/kg: elevated plus maze, light/dark box and marble burying) were performed. Theoretical calculations analyzed interaction of Riparin A with gamma-amino butyric acid (GABA) receptors. Only Riparin A at 2000 mg/kg alter body weight, food and water consumption and urine production after 7 and/or 14 days treatment and increased serum triglycerides. There was increase in the time spent in the open arms (TSOA) and number of transitions between compartments (NTC) and decrease in number of hidden balls (NHB) in Riparin A-treated animals at 200 mg/kg ( P  < 0.05), whose approximate ED 50 was 283.1 (156.5–397.1) mg/kg. The functional amide of Riparin A interacted with the GABA A receptor mainly at subunits α 2 and β 1 and presented strong interaction with the Asp68 residue, which is part of the pharmacophore group. Riparin A was toxically safe and pharmacologically active for anxiolytic purposes, revealed NOAEL of 200 mg/kg and probably interacts with Asp68 residues of benzodiazepine receptors by hydrogen bonds. [ABSTRACT FROM AUTHOR]

Abstract: Studies showing anxiolytic-like properties of natural products have grown. This paper evaluated if carvacryl acetate (CA) could be studied as an alternative drug to treat anxiety disorders. Elevated plus maze (EPM) tests , light-dark box (LDB) tests, and marble-burying tests (MBTs) were performed on mice. In the first protocol, the anxiolytic-like activities of CA 25, 50, 75 and 100mg/kg at single doses were compared to those of the vehicle, buspirone 5mg/kg (BUSP) and diazepam 1mg/kg (DZP). In the second protocol, the anxiolytic-like actions of CA were tested for GABAergic and serotonergic systems. The time spent in the open arms (TSOA) and the number of open arms entries (NOAE) were measured in EPM; the time spent in the light box (TSLB) and the number of entries to light box (NELB) were measured in LDB; and the number of marbles buried (NMB) were measured in MBT. CA increased TSOA and NOAE in the EPM, as well as TSLB and NELB in the LDB and the NMB in the MBT. The anxiolytic-like activity of CA 25; 50; 75 and 100mg/kg was not associated with psychomotor retardation in the open field test and in the Rota rod test, contrarily with what happened with DZP. In the second protocol, to suggest the mechanism of action of CA, flumazenil 25mg/kg ip (FLU) and WAY 100,635 10mg/kg ip (WAY–5-HT1A antagonist) were also used. FLU+CA100 reduced TSOA in the EPM when compared to CA100 but WAY+CA100 did not. In LDB, FLU+CA100 reduced the TSLB when compared to CA100 but WAY+CA100 did not. In the MBT, FLU+CA100 inhibited the effect of CA100 on the NMB but WAY+CA100 did not. In conclusion, CA seems to have an anxiolytic-like effect, probably due to GABAergic agonist action, without psychomotor side effects. [Copyright &y& Elsevier]