RESUMEN
Anxiety disorders are major health problems in terms of costs stemming from sick leave, disabilities, healthcare and premature mortality. Despite the availability of classic anxiolytics, some anxiety disorders are still resistant to treatment, with higher rates of adverse effects. In this respect, several toxins isolated from arthropod venoms are useful in identifying new compounds to treat neurological disorders, particularly pathological anxiety. Thus, the aims of this study were to identify and characterize an anxiolytic peptide isolated from the venom of the social wasp Polybia paulista. The peptide was identified as Polisteskinin R, with nominal molecular mass [M+H](+)=1301Da and primary structure consisting of Ala-Arg-Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg-OH. The anxiolytic effect was tested using the elevated plus maze test. Moreover, adverse effects on the spontaneous behavior and motor coordination of animals were assessed using the open field and rotarod tests. Polisteskinin R induced a dose-dependent anxiolytic effect. Animals treated with the peptide and diazepam spent significantly more time into the open arms when compared to the groups treated with the vehicle and pentylenetetrazole. No significant differences in spontaneous behavior or motor coordination were observed between the groups, showing that the peptide was well tolerated. The interaction by agonists in both known BK receptors induces a variability of physiological effects; Polisteskinin R can act on these receptors, inducing modulatory activity and thus, attenuating anxiety behaviors. The results of this study demonstrated that the compound Polisteskinin R exerted potent anxiolytic effects and its analogues are promising candidates for experimental pharmacology.
Asunto(s)
Ansiolíticos/uso terapéutico , Ansiedad/tratamiento farmacológico , Bradiquinina/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Venenos de Avispas/uso terapéutico , Animales , Ansiolíticos/efectos adversos , Ansiolíticos/aislamiento & purificación , Ansiedad/psicología , Bradiquinina/efectos adversos , Bradiquinina/aislamiento & purificación , Evaluación Preclínica de Medicamentos/métodos , Masculino , Fragmentos de Péptidos/efectos adversos , Fragmentos de Péptidos/aislamiento & purificación , Ratas , Ratas Wistar , Venenos de Avispas/efectos adversos , Venenos de Avispas/aislamiento & purificaciónRESUMEN
BACKGROUND: Arthropod venoms have attracted interest because they represent a source of neuroactive compounds that can be useful tools in neuroscience and pharmacological investigations. OBJECTIVE: The purpose of the present work was to evaluate the anticonvulsant, anxiolytic, and behavioral effects of the peptide fraction separated from venom of the social wasp. MATERIALS AND METHODS: The low- molecular-weight compounds of the venom were separated by ultrafiltration and the bioassays were performed to test anticonvulsant and anxiolytic effects, as well as alterations in the spontaneous behavior of the animals. RESULTS: Intracerebroventricular injections of the compounds induced dose-dependent anticonvulsant effects and a potent anxiolytic activity. Regarding behavioral effects, no significant differences were observed in relation to the saline control group. CONCLUSION: The low-molecular-weight compounds of the venom of Polybia paulista include neuroactive peptides that can be used as pharmacological resources for anticonvulsant and anxiolytic drug research.
RESUMEN
The venom of social wasps has been poorly studied so far, despite the high number of accidents in humans and assessment of the use of these wasps as a biological control of pests. The study of the pharmacological effects of the venom is of great importance since the poisoning is dangerous causing serious systemic effects, including death in the case of multiple attacks. In this study, the pharmacological activities of venom from the social wasp Synoeca cyanea were evaluated by the following assays: LD50 in mice, the behavioural effects and the hemorrhagic activity induced by the venom in mice, the oedematogenic activity in rat, the haemolysis in human blood, the stimulating effect on guinea-pig smooth muscle, and the antimicrobial activity. The aim was to determine the toxic effects of venom and to perform a comparative study with earlier work conducted with venom from other wasp species. Results showed that S. cyanea venom produced a potent dose-dependent oedema, as well as antibacterial and haemolytic activities, suggesting the presence of histamine, serotonin, kinins and other molecules related to increased vascular permeability and cytolytic activity in this venom. Despite previous studies with wasp venoms, S. cyanea venom presented a slight hemorrhagic effect. Data obtained in the smooth muscle assay also suggest the presence of BK or analogues in S. cyanea whole venom. The knowledge of symptoms and effects produced by S. cyanea venom is critical for health organizations, in order to improve clinical treatment in accidents caused by wasp stings.