RESUMEN
ABSTRACT Uliginosin B, a phloroglucinol isolated from Hypericum polyanthemum Klotzsch ex Reichardt, Hypericaceae, has antidepressant-like effect in the forced swimming test in rodents and inhibits monoamines neuronal reuptake without binding to their neuronal carriers. Studies showed the involvement of Na+,K+-ATPase brain activity in depressive disorders, as well as the dependence of neuronal monoamine transport from Na+ gradient generated by Na+,K+-ATPase. This study aimed at evaluating the effect of uliginosin B on Na+,K+-ATPase activity in mice cerebral cortex and hippocampus (1 and 3 h after the last administration) as well as the influence of veratrine, a Na+ channel opener, on the antidepressant-like effect of uliginosin B. Mice were treated (p.o.) with uliginosin B single (10 mg/kg) or repeated doses (10 mg/kg/day, 3 days). Acute administration reduced the immobility in the forced swimming test and tail suspension test and increased Na+,K+-ATPase activity in cerebral cortex 1 h after treating, whereas the repeated treatment induced the antidepressant-like effect and increased the Na+,K+-ATPase activity at both times evaluated. None treatment affected the hippocampus enzyme activity. Veratrine pretreatment prevented uliginosin B antidepressant-like effect in the forced swimming test, suggesting the involvement of Na+ balance regulation on this effect. Altogether, these data indicate that uliginosin B reduces the monoamine uptake by altering Na+ gradient.
RESUMEN
Previously we designed a series of pyridinic anticholinesterasic compounds based on molecular hybridization between tacrine and the natural piperidine alkaloid (-)-3-O-acetylspectaline isolated from Senna spectabilis. Based on the information that the cholinergic system has an important role in the treatment of schizophrenia and depression, we herein report the evaluation of a series of pyridinic compounds in animal models for antipsychotic and antidepressant-like activities. Compound 2 decreased the immobility time of mice in the forced swimming test (5 and 10mg/kg p.o.) and prevented the climbing behavior induced by apomorphine (10mg/kg, p.o.), without impairing animals locomotor activity.
Asunto(s)
Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Piperidinas/síntesis química , Piperidinas/uso terapéutico , Piridinas/síntesis química , Animales , Antidepresivos/síntesis química , Antidepresivos/química , Antidepresivos/farmacología , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Ratones , Piperidinas/química , Piperidinas/farmacología , Piridinas/química , Piridinas/farmacología , Esquizofrenia/tratamiento farmacológicoRESUMEN
CONTEXT: Hypericum caprifoliatum Cham & Schlecht (Guttiferae) extracts have a potential antidepressant-like effect in rodents. However, the molecular mechanisms by which these extracts exert this effect remain unclear. OBJECTIVE: This study evaluated the effect of HC1, a fraction obtained from H. caprifoliatum enriched in phloroglucinol derivatives, on the Naâº, K⺠ATPase activity in mouse brain and verified the influence of veratrine on the effect of HC1 in the forced swimming test (FST). MATERIALS AND METHODS: Veratrine (0.06 mg/kg) and HC1 (360 mg/kg) were given alone or combined i.p. 60 and p.o. 30 min, respectively, before FST. The effect of single and repeated administration (once a day for 3 consecutive days) of HC1 (360 mg/kg) on Naâº, K⺠ATPase activity was evaluated ex vivo in the cerebral cortex and hippocampus of mice subjected or not to FST. RESULTS: HC1 reduced the immobility time (103.15 ± 18.67 s), when compared to the control group (183.6 ± 9.51 s). This effect was prevented by veratrine (151.75 ± 22.19 s). Mice repeatedly treated with HC1 presented a significant increase in Naâº, K⺠ATPase activity, both in cerebral cortex (46 ± 2.41 nmol Pi/min·mg protein) and hippocampus (49.83 ± 2.31 nmol Pi/min·mg protein), in relation to the respective controls (30 ± 2.66 and 29.83 ± 2.31 nmol Pi/min·mg protein respectively). DISCUSSION AND CONCLUSION: The HC1 antidepressant-like effect on FST might be related to its capacity to inhibit Na⺠influx. HC1 increases hippocampal and cortical Naâº, K⺠ATPase activities possibly through long-term regulatory mechanisms.
Asunto(s)
Antidepresivos/farmacología , Depresión/tratamiento farmacológico , Floroglucinol/farmacología , Extractos Vegetales/farmacología , Animales , Antidepresivos/administración & dosificación , Antidepresivos/aislamiento & purificación , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hypericum , Masculino , Ratones , Floroglucinol/administración & dosificación , Floroglucinol/aislamiento & purificación , Extractos Vegetales/administración & dosificación , Sodio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Natación , Veratrina/administración & dosificación , Veratrina/farmacologíaRESUMEN
In this study, we evaluated the effects of three simple organochalcogenides (diphenyl diselenide, diphenyl ditelluride and diphenyl telluride) and ebselen on the glutamate-driven 45Ca2+ influx into chick embryonic retinal cells, as well as their effects on the excitotoxic injury in retina cells. None of the compounds tested interfered with basal 45Ca2+ uptake. Diphenyl diselenide and diphenyl ditelluride had no effects on glutamate-driven 45Ca2+ influx. Diphenyl telluride (100-400 microM) decreased and ebselen (100-400 microM) completely blocked the glutamate-driven 45Ca2+ influx (P < 0.01) into chick retinal explants. The assessment of neural injury was made spectrophotometrically by quantification of cellularly reduced MTT (3(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) 24 h after the beginning of glutamate exposure (8 h). Ebselen had no effects on retinal MTT reduction when co-incubated with glutamate for 8 h. However, when ebselen (100 and 400 microM) was co-incubated for 8 h with glutamate and remained in the incubation media until MTT evaluation (24 h after the beginning of incubation), it protected retinal cells against the decrease in MTT reduction induced by glutamate. These data indicate that besides its capacity of interacting with Ca2+ channels, other mechanisms are involved in the neuroprotection afforded by ebselen in this work, possibly its antioxidant properties.