RESUMO
Ortho-eugenol is a synthetic derivative from eugenol, the major compound of clove essential oil, which has demonstrated antidepressant and antinociceptive effects in pioneering studies. Additionally, its effects appear to be dependent on the noradrenergic and dopaminergic systems. Depression and anxiety disorders are known to share a great overlap in their pathophysiology, and many drugs are effective in the treatment of both diseases. Furthermore, high levels of anxiety are related to working memory deficits and increased oxidative stress. Thus, in this study we investigated the effects of acute treatment of ortho-eugenol, at 50, 75 and 100 mg/kg, on anxiety, working memory and oxidative stress in male Swiss mice. Our results show that the 100 mg/kg dose increased the number of head-dips and reduced the latency in the hole-board test. The 50 mg/kg dose reduced malondialdehyde levels in the prefrontal cortex and the number of Y-maze entries compared to the MK-801-induced hyperlocomotion group. All doses reduced nitrite levels in the hippocampus. It was also possible to assess a statistical correlation between the reduction of oxidative stress and hyperlocomotion after the administration of ortho-eugenol. However, acute treatment was not able to prevent working memory deficits. Therefore, the present study shows that ortho-eugenol has an anxiolytic and antioxidant effect, and was able to prevent substance-induced hyperlocomotion. Our results contribute to the elucidation of the pharmacological profile of ortho-eugenol, as well as to direct further studies that seek to investigate its possible clinical applications.
Assuntos
Eugenol , Memória de Curto Prazo , Masculino , Animais , Camundongos , Eugenol/farmacologia , Eugenol/uso terapêutico , Ansiedade/tratamento farmacológico , Transtornos de Ansiedade , Estresse Oxidativo , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Óleo de CravoRESUMO
Ortho-eugenol is a synthetic derivative from eugenol, the major compound of clove essential oil, which has demonstrated antidepressant and antinociceptive effects in pioneering studies. Additionally, its effects appear to be dependent on the noradrenergic and dopaminergic systems. Depression and anxiety disorders are known to share a great overlap in their pathophysiology, and many drugs are effective in the treatment of both diseases. Furthermore, high levels of anxiety are related to working memory deficits and increased oxidative stress. Thus, in this study we investigated the effects of acute treatment of ortho-eugenol, at 50, 75 and 100 mg/kg, on anxiety, working memory and oxidative stress in male Swiss mice. Our results show that the 100 mg/kg dose increased the number of head-dips and reduced the latency in the hole-board test. The 50 mg/kg dose reduced malondialdehyde levels in the prefrontal cortex and the number of Y-maze entries compared to the MK-801-induced hyperlocomotion group. All doses reduced nitrite levels in the hippocampus. It was also possible to assess a statistical correlation between the reduction of oxidative stress and hyperlocomotion after the administration of ortho-eugenol. However, acute treatment was not able to prevent working memory deficits. Therefore, the present study shows that ortho-eugenol has an anxiolytic and antioxidant effect, and was able to prevent substance-induced hyperlocomotion. Our results contribute to the elucidation of the pharmacological profile of ortho-eugenol, as well as to direct further studies that seek to investigate its possible clinical applications.
Ortho-eugenol é um derivado sintético do eugenol, composto principal do óleo essencial de cravo, que demonstrou efeitos antidepressivos e antinociceptivos em estudos pioneiros. Além disso, seus efeitos parecem ser dependentes dos sistemas noradrenérgico e dopaminérgico. Sabe-se que os transtornos de depressão e ansiedade compartilham uma grande sobreposição em sua fisiopatologia, e muitas drogas são eficazes no tratamento de ambas as doenças. Além disso, altos níveis de ansiedade estão relacionados a déficits de memória de trabalho e aumento do estresse oxidativo. Assim, o presente estudo investigou os efeitos do tratamento agudo de orto-eugenol, nas doses de 50, 75 e 100 mg/kg, na ansiedade, memória de trabalho e estresse oxidativo em camundongos Swiss machos. Nossos resultados mostram que a dose de 100 mg/kg aumentou o número de mergulhos e reduziu a latência no teste da placa perfurada. A dose de 50 mg/kg reduziu os níveis de malondialdeído no córtex pré-frontal e o número de entradas no labirinto em Y em comparação com o grupo de hiperlocomoção induzida por MK-801. Todas as doses reduziram os níveis de nitrito no hipocampo. Também foi possível avaliar uma correlação estatística entre a redução do estresse oxidativo e a hiperlocomoção após a administração do orto-eugenol. No entanto, o tratamento agudo não foi capaz de prevenir os déficits de memória de trabalho. Portanto, o presente estudo mostra que o orto-eugenol tem efeito ansiolítico e antioxidante, sendo capaz de prevenir a hiperlocomoção induzida pela substância. Nossos resultados contribuem para a elucidação do perfil farmacológico do orto-eugenol, bem como para direcionar novos estudos que busquem investigar suas possíveis aplicações clínicas.
Assuntos
Animais , Camundongos , Ansiedade/tratamento farmacológico , Eugenol , Óleos Voláteis , Estresse Oxidativo/efeitos dos fármacosRESUMO
Leishmaniasis is a group of important parasitic diseases affecting millions worldwide. To understand more clearly the quality of T helper type 1 (Th1) response stimulated after Leishmania infection, we applied a multiparametric flow cytometry protocol to evaluate multifunctional T cells induced by crude antigen extracts obtained from promastigotes of Leishmania braziliensis (LbAg) and Leishmania amazonensis (LaAg) in peripheral blood mononuclear cells from healed cutaneous leishmaniasis patients. Although no significant difference was detected in the percentage of total interferon (IFN)-γ-producing CD4(+) T cells induced by both antigens, multiparametric flow cytometry analysis revealed clear differences in the quality of Th1 responses. LbAg induced an important proportion of multifunctional CD4(+) T cells (28% of the total Th1 response evaluated), whereas LaAg induced predominantly single-positive cells (68%), and 57% of those were IFN-γ single-positives. Multifunctional CD4(+) T cells showed the highest mean fluorescence intensity (MFI) for the three Th1 cytokines assessed and MFIs for IFN-γ and interleukin-2 from those cells stimulated with LbAg were significantly higher than those obtained after LaAg stimulation. These major differences observed in the generation of multifunctional CD4(+) T cells suggest that the quality of the Th1 response induced by L. amazonensis antigens can be involved in the mechanisms responsible for the high susceptibility observed in L. amazonensis-infected individuals. Ultimately, our results call attention to the importance of studying a Th1 response regarding its quality, not just its magnitude, and indicate that this kind of evaluation might help understanding of the complex and diverse immunopathogenesis of American tegumentary leishmaniasis.