RESUMO
RATIONALE: (Octylseleno)-xylofuranoside (OSX) is an organoselenium compound from the class of alkylseleno carbohydrates possessing a C8 alkyl chain. Members of this class of organoselenium compounds have promising pharmacological activities, among them are antioxidant and acute antidepressant-like activities with the involvement of monoaminergic system, as previously presented by our research group. OBJECTIVE: The objective of the study was to investigate the possible involvement of cellular signalling pathways in the antidepressant-like effect caused by OSX (0.01 mg/kg, oral route (p.o.) by gavage) in the tail suspension test (TST) in mice. METHODS: Mice were treated by intracerebroventricular (i.c.v.) injection either with vehicle or with H-89 (1 µg/site i.c.v., an inhibitor of protein kinase A-PKA), KN-62 (1 µg/site i.c.v., an inhibitor of Ca2+/calmodulin-dependent protein kinase II-CAMKII), chelerythrine (1 µg/site i.c.v., an inhibitor of protein kinase C-PKC) or PD098059 (5 µg/site i.c.v., an inhibitor of extracellular-regulated protein kinase 1/2-ERK1/2). Fifteen minutes after, vehicle or OSX was injected, and 30 min later, the TST and open field tests (OFT) were carried out. RESULTS: The antidepressant-like effect of orally administered OSX was blocked by treatment of the mice with H-89, KN-62, chelerythrine and PD098059; all inhibitors of signalling proteins involved with neurotrophic signalling pathways. The number of crossings in the OFT was not altered by treatment with OSX and/or signalling antagonists. CONCLUSIONS: The results demonstrated that OSX showed an antidepressant-like effect in the TST in mice through the activation of protein kinases PKA, PKC, CAMKII and ERK1/2 that are involved in intracellular signalling pathways.
Assuntos
Antidepressivos/farmacologia , Glicosídeos/farmacologia , Compostos Organosselênicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Antidepressivos/uso terapêutico , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Glicosídeos/uso terapêutico , Elevação dos Membros Posteriores/métodos , Isoquinolinas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Compostos Organosselênicos/uso terapêutico , Proteína Quinase C/metabolismo , Sulfonamidas/farmacologiaRESUMO
The objective of this work was to evaluate the effects of standardized hydroalcholic extract of Commiphora mukul (HECM) in animal model of chronic stress medicated depression, namely olfactory bulbectomy (OBX) model in rats. Effects of 14-day (subacute) oral pretreatment of HECM (50, 100 and 200 mg/kg) were evaluated on depression and stress related parameters on OBX rats. Separate groups for sham control, OBX control and positive controls namely imipramine (20 mg/kg), fluoxetine (30 mg/kg) and desipramine (15 mg/kg) were also maintained. Behavioral and physiological parameters in open field and elevated plus maze were recorded. HECM showed dose-dependent reversal of OBX-induced physiological effects such as reduction of body weight, body temperature, heart rate and serum sodium concentration. HECM also showed reversal effects on OBX induced food intake increase and hyperactivity in open field and elevated plus maze paradigm. In conclusion, HECM demonstrated restorative effects in OBX induced depression model in rats probably due to stress reliving mechanisms.
RESUMO
Chronic stressful stimuli influence disease susceptibility to depression, cardiovascular, metabolic and neurodegenerative disorders. The present work investigated antidepressant and antioxidant properties of the aqueous extract from Cecropia pachystachya in a mouse model of chronic unpredictable stress (CUS). Our results indicated that acute administration of the aqueous extract (AE) from C. pachystachya (200 and 400mg/kg, p.o.) produced an antidepressant-like effect in the forced swimming test (FST). The chronic treatment with C. pachystachya extract (200mg/kg, p.o., for 14 days) prevented the depressant-like effect but not the anxiogenic effect induced by CUS. In addition to the behavioral modifications, the 14 days of CUS increased lipid peroxidation in the hippocampus (HP) and prefrontal cortex (PFC), decreased total thiol content and glutathione peroxidase activity in the HP. C. pachystachya AE administration during CUS protocol was able to prevent the oxidative damage induced by stress. However, no changes were observed in the activity of the antioxidant enzymes superoxide dismutase and catalase in the above cited brain areas after the stress protocol and treatment. Our results suggest that C. pachystachya prevented both depressive behavior and oxidative damage induced by CUS, supporting its neuroprotective potential against behavioral and biochemical dysfunctions induced by chronic stress.
Assuntos
Antidepressivos/farmacologia , Cecropia , Depressão/prevenção & controle , Extratos Vegetais/farmacologia , Estresse Psicológico/prevenção & controle , Animais , Antidepressivos/administração & dosagem , Ansiedade/prevenção & controle , Doença Crônica , Modelos Animais de Doenças , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Extratos Vegetais/administração & dosagemRESUMO
Antidepressant, anti-inflammatory, antihypoxic and antioxidant activities of methanol extract of Juglans regia L., Juglandaceae, flower were investigated. Antidepressant activity was examined by forced swimming test and tail suspension test in mice. Antihypoxic activity was investigated in haemic and circulatory models. The effects were pronounced in both models. It produced statistically significant anti-inflammatory activity in carrageenan induced edema at nearly all doses, compared to control groups. IC50 for DPPH radical-scavenging activity was 674±27.6 µg mL-1. Extract showed good Fe2+ chelating ability (IC50 43±1.5 µg mL-1). It exhibited low antioxidant activity in linoleic acid peroxidation test. Its pharmacological effects may be attributed, in part, to the presence of phenols and ISSN 0102-695X flavonoids in the extract.
RESUMO
A proposta deste trabalho foi de avaliar os efeitos da fração de alcalóides terciários totais (TTAF) de Cissampelos sympodialis Eichler (Menispermaceae) em dois modelos animais de depressão: a) teste do nado forçado e b) teste da reserpina. O tratamento de camundongos com TTAF (12,5 mg/kg) reduziu o tempo total de imobilidade dos animais. Também reverteu a hipotermia induzida por reserpina, demonstrando um efeito antidepressivo nos dois modelos. Adicionalmente, o tratamento com TTAF não modificou a ambulação e o comportamento de levantar das patas dianteiras dos animais avaliados no teste do campo aberto, realizado no intuito de investigar se a redução no tempo de imobilidade apresentada no teste do nado forçado foi causada por estimulação na atividade locomotora. Como a warifteína é um dos principais alcalóides presente na TTAF da C. sympodialis, e tem atividade inibidora da enzima fosfodiesterase, ela pode ser responsável pelo efeito antidepressivo observado na fração estudada.
The purpose of the present study was to evaluate the effects of total tertiary alkaloid fraction (TTAF) of Cissampelos sympodialis Eichler (Menispermaceae) on two animal models of depression: a) forced swim test and b) reserpine test. Treatment of mice with TTAF (12.5 mg/kg) reduced the total immobility time. It also reversed the reserpine-induced hypothermia, demonstrating an antidepressant effect in both models. Additionally, TTAF treatment did not modify the ambulation and rearing evaluated in open field test in order to investigate if the immobility time reduction found in the forced swimming test was caused by locomotive activity stimulation. Since warifteine is one of the main alkaloids present in the TTAF of C. sympodialis, and it has inhibitory activity of the phosphodiesterase enzyme, it may be responsible by the antidepressant effect found in the fraction studied.