RESUMO
BACKGROUND: Central nervous system disorders such as anxiety, depression and epilepsy are characterized by sharing several molecular mechanisms in common and the involvement of the L-arginine/NO pathway in neurobehavioral studies with ß-caryophyllene is still little discussed. OBJECTIVES: One of the objectives of the present study was to demonstrate the anxiolytic behavioral effect of ß-caryophyllene (ß-CBP) in female Swiss mice, as well as to investigate the molecular mechanisms underlying the results obtained. METHODS: This study evaluated the neurobehavioral effects of ß-CBP using the open field test, rota- rod test, elevated plus maze test, novelty suppressed feeding test, tail suspension test and forced swim test, as well as pilocarpine, pentylenetetrazole and isoniazid-induced epileptic seizure models. RESULTS: The results demonstrated that the neuropharmacological activities of ß-CBP may involve benzodiazepine/GABAergic receptors, since the pre-treatment of ß-CBP (200 mg/kg) associated with flumazenil (5 mg/kg, benzodiazepine receptor antagonist) and bicuculline (1 mg/kg, selective GABAA receptor antagonist) reestablished the anxiety parameters in the elevated plus-maze test, as well as the results of reduced latency to consume food in the novelty suppressed feeding test. In addition to benzodiazepine/GABAergic receptors, the neuropharmacological properties of ß-CBP may be related to inhibition of nitric oxide synthesis, since pre-treatment with L-arginine (500-750 mg/kg) reversed significantly the anxiolytic, antidepressant and anticonvulsant activities of ß-CBP. CONCLUSION: The results obtained provide additional support in understanding the neuromolecular mechanisms underlying the anxiolytic, antidepressant and anticonvulsive properties of ß-CBP in female Swiss mice.
Assuntos
Ansiolíticos/química , Anticonvulsivantes/química , Antidepressivos/química , Antagonistas de Receptores de GABA-A/química , Sesquiterpenos Policíclicos/química , Animais , Ansiolíticos/farmacologia , Anticonvulsivantes/farmacologia , Antidepressivos/farmacologia , Arginina , Comportamento Animal , Benzodiazepinas/metabolismo , Bicuculina/química , Bicuculina/farmacologia , Feminino , Flumazenil/química , Flumazenil/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Humanos , Aprendizagem em Labirinto , Camundongos , Óxido Nítrico/metabolismo , Sesquiterpenos Policíclicos/farmacologia , Receptores de GABA-A/metabolismo , Convulsões/induzido quimicamente , Transdução de SinaisRESUMO
Praziquantel is currently the only drug available to treat schistosomiasis, a disease of enormous public health significance caused by a blood fluke of the genus Schistosoma Diminazene, a drug approved by the FDA, has been successfully used to treat diseases caused by blood protozoan parasites. In this study, we evaluated the antiparasitic properties of diminazene against Schistosoma mansoniex vivo and in mice harboring either chronic or early S. mansoni infections. In vitro, we monitored phenotypic and tegumental changes as well as the effects of the drug on pairing and egg production. In mice infected with either adult (chronic infection) or immature (early infection) worms, diminazene was administered intraperitoneally (10 to 100 mg/kg of body weight) or by oral gavage (100 to 400 mg/kg), and we studied the influence of the drug on worm burden and egg production. Liver and spleen pathologies and serum aminotransferase levels were also analyzed. In vitro, 50% effective concentrations (EC50) and EC90 revealed that diminazene is able to kill both immature and adult parasites, and its effect was time and concentration dependent. In addition, confocal laser scanning microscopy showed morphological alterations in the teguments of schistosomes. In an animal model, the influence of the drug on worm burden, egg production, hepatomegaly, and splenomegaly depended on the dosing regimen applied and the route of administration. Diminazene also caused a significant reduction in aminotransferase levels. Comparatively, diminazene treatment was more effective in chronic infection than in early infection. In tandem, our study revealed that diminazene possesses anthelmintic properties and inhibits liver injury caused by Schistosoma eggs.
Assuntos
Parasitos , Esquistossomose mansoni , Esquistossomose , Animais , Diminazena/análogos & derivados , Diminazena/farmacologia , Camundongos , Schistosoma mansoni , Esquistossomose mansoni/tratamento farmacológicoRESUMO
BACKGROUND: Bergenin, a compound derived from gallic acid, is a secondary metabolite of the plant Peltophorum dubium (Spreng.) Taub. OBJECTIVE: In this study, we aimed to characterize the ability of bergenin to eliminate the radicals in non-biological systems. METHODS: We evaluated bergenin's ability to protect erythrocytes from oxidative damage in a biological system. We have elucidated bergenin structure using nuclear magnetic resonance, X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry. We then evaluated its antioxidant capacity in vitro against DPPHâ¢, ABTSâ¢+, hydroxyl radicals, and nitric oxide, and determined its ability to transfer electrons owing to its reduction potential and ability to chelate iron. We also evaluated its protective capacity against oxidative damage produced by AAPH in erythrocytes, its hemolytic properties, its ability to inhibit hemolysis, and its ability to maintain intracellular reduced glutathione homeostasis. RESULTS: Bergenin concentrations between 0.1 and 3mM significantly (p < 0.05) and dose dependently decreased formation of ABTSâ¢+, DPPHâ¢, nitrite ions, OHâ¢, reduced formation ferricyanide, ferrozine-Fe2+complex, inhibited AAPH-induced oxidative hemolysis of erythrocytes, raised GSH levels in the presence of AAPH, inhibited AAPH-induced lipid peroxidation in erythrocytes. CONCLUSION: Bergenin may represent a novel alternative antioxidant, with potential applications in various industries, including drugs, cosmetics, and foods.
Assuntos
Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Benzopiranos/isolamento & purificação , Benzopiranos/farmacologia , Eritrócitos/efeitos dos fármacos , Fabaceae/química , Animais , Antioxidantes/química , Benzopiranos/química , Benzotiazóis/química , Compostos de Bifenilo/química , Transporte de Elétrons/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Glutationa/metabolismo , Hemólise/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Radical Hidroxila/química , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Ferro/química , Peroxidação de Lipídeos/efeitos dos fármacos , Modelos Moleculares , Conformação Molecular , Nitritos/química , Picratos/química , Ratos , Ratos Wistar , Ácidos Sulfônicos/químicaRESUMO
Schistosomiasis is a neglected tropical disease that affects hundreds of millions of people worldwide. Since the treatment of this disease currently relies on a single drug, praziquantel, new and safe schistosomicidal agents are urgently required. Nerolidol, a sesquiterpene present in the essential oils of several plants, is found in many foods and was approved by the U.S. Food and Drug Administration. In this study we analysed the in vitro antiparasitic effect of nerolidol on Schistosoma mansoni adult worms. Nerolidol at concentrations of 31.2 and 62.5 µM reduced the worm motor activity and caused the death of all male and female schistosomes, respectively. In addition, confocal laser scanning microscopy revealed morphological alterations on the tegument of worms such as disintegration, sloughing and erosion of the surface, and a correlation between viability and tegumental damage was observed. In conclusion, nerolidol may be a promising lead compound for the development of antischistosomal natural agents.