RESUMO
Polyphenols have neuroprotective effects after brain ischemia. It has been demonstrated that rosmarinic acid (RA), a natural phenolic compound, possesses antioxidant and anti-inflammatory properties. To evaluate the effectiveness of RA against memory deficits induced by permanent middle cerebral artery occlusion (pMCAO) mice were treated with RA (0.1, 1, and 20mg/kg/day, i.p. before ischemia and during 5 days). Animals were evaluated for locomotor activity and working memory 72 h after pMCAO, and spatial and recognition memories 96 h after pMCAO. In addition, in another set of experiments brain infarction, neurological deficit score and myeloperoxidase (MPO) activity were evaluates 24h after the pMCAO. Finally, immunohistochemistry, and western blot, and ELISA assay were used to analyze glial fibrillary acidic protein (GFAP), and synaptophysin (SYP) expression, and BDNF level, respectively. The working, spatial, and recognition memory deficits were significantly improved with RA treatment (20mg/kg). RA reduced infarct size and neurological deficits caused by acute ischemia. The mechanism for RA neuroprotection involved, neuronal loss suppression, and increase of synaptophysin expression, and increase of BDNF. Furthermore, the increase of MPO activity and GFAP immunireactivity were prevented in MCAO group treated with RA. These results suggest that RA exerts memory protective effects probably due to synaptogenic activity and anti-inflammatory action.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Cinamatos/farmacologia , Depsídeos/farmacologia , Transtornos da Memória/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Astrócitos/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Gliose/tratamento farmacológico , Gliose/etiologia , Gliose/patologia , Gliose/fisiopatologia , Infarto da Artéria Cerebral Média , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/patologia , Transtornos da Memória/fisiopatologia , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Camundongos , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Peroxidase/metabolismo , Reconhecimento Psicológico/efeitos dos fármacos , Reconhecimento Psicológico/fisiologia , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia , Sinapses/efeitos dos fármacos , Sinapses/patologia , Sinapses/fisiologia , Ácido RosmarínicoRESUMO
Brain ischemia pathophysiology involves a complex cascade of events such as inflammation and oxidative stress that lead to neuronal loss and cognitive deficits. Caffeic acid (CA) is a natural phenolic compound with antioxidant and anti-inflammatory properties. To evaluate the neuroprotective efficacy of this compound in mice subjected to a permanent middle cerebral artery occlusion, animals were pretreated and post-treated with CA, 2, 20, and 60 mg/kg/day, intraperitoneally, at 24, 48, 72, 96, or 120 h after ischemia. Animals were evaluated at 24 h after the permanent middle cerebral artery occlusion for brain infarction and neurological deficit score. At 72 h after the occlusion, animals were evaluated for locomotor activity, working memory, and short-term aversive memory; long-term aversive memory was evaluated 24 h after the evaluation of short-term aversive memory. Finally, at 120 h after the event, spatial memory and the expression levels of synaptophysin (SYP), SNAP-25, and caspase 3 were evaluated. The treatment with CA reduced the infarcted area and improved neurological deficit scores. There was no difference in locomotor activity between groups. The working, spatial, and long-term aversive memory deficits improved with CA. Furthermore, western blotting data showed that the expression of SYP, which correlates with synaptic formation and function, decreased after ischemic insult, and CA inhibited the reduction of SYP expression. Ischemia also increased, and CA treatment decreased, caspase 3 expression. These results suggest that CA exerts neuroprotective and antidementia effects, at least in part, by preventing the loss of neural cells and synapses in ischemic brain injury.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Ácidos Cafeicos/farmacologia , Transtornos da Memória/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Animais , Isquemia Encefálica/complicações , Isquemia Encefálica/fisiopatologia , Ácidos Cafeicos/administração & dosagem , Caspase 3/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Infarto da Artéria Cerebral Média/complicações , Masculino , Transtornos da Memória/etiologia , Camundongos , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Sinaptofisina/genética , Proteína 25 Associada a Sinaptossoma/genética , Fatores de TempoRESUMO
OBJECTIVE: The purpose of this study was to investigate the effect of vitamin E on alveolar bone loss (ABL) and anxiety in rats with ligature-induced experimental periodontitis (EP). MATERIAL AND METHODS: Wistar rats were subjected to ligature-induced EP and treated with vitamin E (500mg/kg, orally) for 9 days. Then anxiety was tested using the elevated plus-maze (EPM) test. All of the animals were euthanised by cervical dislocation on day 11. ABL was analysed morphometrically and histopathologically. Lipid peroxidation quantification, activity of the enzyme superoxide dismutase and immunohistochemistry to tumour necrosis factor-alpha (TNF-α) and inducible isoform of nitric oxide synthases (iNOS) were also tested. RESULTS: EP induced a marked inflammatory process and intense ABL. Treatment with vitamin E decreased inflammatory reaction, prevented malondialdehyde formation and reduced the immunoreactivity to iNOS, but did not decrease ABL. Vitamin E had an anxiogenic effect on rats with or without EP. CONCLUSIONS: Vitamin E may have potential to reduce oxidative damage and inflammatory response in EP but does not prevent ABL. Attention should be given to indiscriminate use of vitamin E due to the risk of causing anxiety in patients.
Assuntos
Perda do Osso Alveolar/prevenção & controle , Ansiedade/induzido quimicamente , Periodontite/tratamento farmacológico , Vitamina E/uso terapêutico , Perda do Osso Alveolar/patologia , Animais , Comportamento Animal/efeitos dos fármacos , Imuno-Histoquímica , Mediadores da Inflamação/análise , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/análise , Óxido Nítrico Sintase Tipo II/análise , Distribuição Aleatória , Ratos , Ratos Wistar , Superóxido Dismutase/análise , Fator de Necrose Tumoral alfa/análise , Vitamina E/efeitos adversosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Validate the popular use of Plectranthus grandis in gastric disorders through the active components. AIMS: Isolation of barbatusin (BB) and 3beta-hydroxy-3-deoxibarbatusin (BBOH), diterpenes from Plectranthus grandis, and evaluation of their gastroprotective effect and possible mechanisms of action. MATERIALS AND METHODS: Isolation and chemical characterization of diterpenes from Plectranthus grandis by chromatographic and spectroscopic methods and evaluation of gastroprotective action of the diterpenes through ethanol-induced gastric injury in mice model. It was evaluated the effect of capsazepine, indomethacin and the role of nitric oxide and K(ATP-) channels on the gastroprotective effect of BBOH and BB. Additionally it was measured the concentrations of gastric mucus, non-proteic-sulfhydryl groups and total thiobarbituric acid-reactive substances. RESULTS: Orally administered BBOH and BB at doses of 5 and 10mg/kg, markedly reduced the gastric lesions by 59 and 96%, and 32 and 76%, respectively, with superior results as compared to N-acetylcysteine (150 mg/kg, i.p.), reference compound that caused 85% lesion suppression. Although BBOH presented a higher gastroprotection than BB they act by similar mechanisms in relation to N-acetylcysteine, and prevent the depletion of gastric mucus, gastric mucosal non-proteic-sulfhydryl groups as well as the increase in thiobarbituric acid-reactive species. Moreover, the gastroprotective effect of BB was effectively blocked in mice pretreated with TRPV1 antagonist capsazepine, by the non-selective cyclooxygenase inhibitor indomethacin, or by the nitric oxide synthase inhibitor L-NAME but not by K(+)(ATP) channel inhibitor glibenclamide. In contrast, the gastroprotective effect of BBOH was blocked only by indomethacin and glibenclamide pretreatments. CONCLUSION: The protective role for BBOH and BB affording gastroprotection against gastric damage induced by ethanol indicates that these compounds contribute for the activity of Plectranthus species. The different modes of action are probably related to differences in their chemical structure.