RESUMO
Fibrillar aggregates of amyloid beta-peptides are major constituents of the plaques found in the brains of patients with Alzheimer's disease, and have been implicated in the neurotoxicity of Alzheimer's. We previously reported that the methanol extract of mulberry leaves inhibits the formation of amyloid beta-peptide (1-42)-fibrils in vitro, and protects hippocampal neurons from amyloid beta-peptide (1-42)-induced cell death. In this study, we identified antiamyloidogenic substances, pheophorbide a, kaempferol -3-O-glucoside, and kaempferol -3-O-(6-malonyl) glucoside, from the methanol extract of mulberry leaves. We also compared the antiamyloidogenic activity of pheophorbide a with that of other porphyrin-related compounds.
Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Clorofila/análogos & derivados , Glucosídeos/química , Quempferóis/química , Monossacarídeos/química , Morus/química , Fragmentos de Peptídeos/antagonistas & inibidores , Folhas de Planta/química , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Clorofila/química , Clorofila/isolamento & purificação , Cromatografia , Cromatografia Líquida de Alta Pressão , Glucosídeos/isolamento & purificação , Humanos , Quempferóis/isolamento & purificação , Espectrometria de Massas , Metanol/química , Monossacarídeos/isolamento & purificação , Ressonância Magnética Nuclear Biomolecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Porfirinas/química , Multimerização Proteica/efeitos dos fármacosRESUMO
We present efficient syntheses of serofendic acids A and B (SA-A and SA-B), novel neuroprotective substances isolated from fetal calf serum. Biological and pharmacological evaluation showed that SA-A and SA-B have potent protective action against glutamate-induced neurotoxicity, but do not interact directly with glutamate receptors. A pharmacokinetic study showed that they have good oral bioavailability in rats. The results indicate that SA-A and SA-B are potential lead compounds for candidate drugs to treat various neurological disorders.
Assuntos
Diterpenos/síntese química , Diterpenos/farmacologia , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/farmacologia , Administração Oral , Animais , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Cristalografia por Raios X , Diterpenos/administração & dosagem , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Sangue Fetal/química , Ácido Glutâmico/toxicidade , Injeções Intravenosas , Modelos Moleculares , Conformação Molecular , Neurônios/citologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Ratos , Ratos Sprague-Dawley , Estereoisomerismo , Relação Estrutura-Atividade , Distribuição TecidualRESUMO
Mulberry leaf has been reported to possess medicinal properties, including hypoglycemic, hypotensive and diuretic effects. Little is known, however, about its medicinal properties for central nervous system disorders, including Alzheimer's disease. Accumulating evidence suggests that amyloid beta-peptide (1-42) plays an important role in the etiology of Alzheimer's disease. Here we show that mulberry leaf extract inhibits the amyloid beta-peptide (1-42) fibril formation by both the thioflavin T fluorescence assay and atomic force microscopy. Furthermore, mulberry leaf extract protected hippocampal neurons against amyloid beta-peptide (1-42)-induced cell death in a concentration-dependent manner. These results suggest that mulberry leaf extract provides a viable treatment for Alzheimer's disease through the inhibition of amyloid beta-peptide (1-42) fibril formation and attenuation of amyloid beta-peptide (1-42)-induced neurotoxicity.