RESUMO
Systemic administration of 3-nitropropionic acid (3-NPA) is commonly used to induce Huntington's disease (HD)-like symptoms in experimental animals. Here, the potential neuroprotective efficiency of rutin and selenium (RSe) co-administration on 3-NPA-induced HD-like symptoms model in mice was investigated. 3-NPA injection evoked severe alterations in redox status, as indicated via increased striatal malondialdehyde and nitric oxide levels, accompanied by a decrease in levels of antioxidant molecules including glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase. Moreover, 3-NPA potentiated inflammatory status by enhancing the production of interleukin-1ß, tumor necrosis factor-α, and myeloperoxidase activity. Pro-apoptotic cascade was also recorded in the striatum as evidenced through upregulation of cleaved caspase-3 and Bax, and downregulation of Bcl-2. 3-NPA activated astrocytes as indicated by the upregulated glial fibrillary acidic protein and inhibited brain-derived neurotrophic factor. Furthermore, perturbations in cholinergic and monoaminergic systems were observed. RSe provided neuroprotective effects by preventing body weight loss, oxidative stress, neuroinflammation, and the apoptotic cascade. RSe inhibited the activation of astrocytes, increased brain-derived neurotrophic factor, and improved cholinergic and monoaminergic transmission following 3-NPA intoxication. Taken together, RSe co-administration may prevent or delay the progression of HD and its associated impairments through its antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory effects.
Assuntos
Doença de Huntington/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Rutina/farmacologia , Selênio/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Caspase 3 , Catalase/metabolismo , Corpo Estriado/metabolismo , Regulação para Baixo , Sinergismo Farmacológico , Proteína Glial Fibrilar Ácida/biossíntese , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Doença de Huntington/induzido quimicamente , Doença de Huntington/metabolismo , Interleucina-1beta/biossíntese , Masculino , Malondialdeído/metabolismo , Camundongos , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/metabolismo , Nitrocompostos , Peroxidase/metabolismo , Propionatos , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Superóxido Dismutase/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese , Regulação para Cima , Proteína X Associada a bcl-2/biossínteseRESUMO
This study attempts to elucidate the secondary metabolite profiles of Ficus lyrata leaves and fruits grown in Egypt. Non-targeted metabolite profiling via ultra performance liquid chromatography (UPLC)-qTOF-MS was used to identify various chemical classes in F. lyrata fruits and leaves (i.e. flavonoids, phenolic acids and fatty acids) analysed by chemometrics. A total of 72 metabolites were evaluated via a UPLC-qTOF-MS-based metabolomic study. Seventeen flavonoids were characterised and tentatively identified with the main constituents being catechins/procyanidins, O- and C-linked flavonoid glycosides. The major procyanidins were dimers and trimers comprising (epi)catechin and (epi)afzelechin units, whereas the predominant flavones were C-glycosides of luteolin and apigenin. Aside from these major flavonoid classes, a group of benzoic acids, caffeoylquinic acids, fatty acid and sphingolipids were also annotated. This study provides the most complete map for polyphenol distribution in F. lyrata leaves and fruits and the basis for future investigation of its fruits nutritional value or possible nutraceutical uses.
Assuntos
Ficus/química , Apigenina/análise , Benzoatos/análise , Biflavonoides/análise , Catequina/análise , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Egito , Ácidos Graxos/química , Flavonas/análise , Flavonoides/análise , Frutas/química , Glicosídeos/análise , Estrutura Molecular , Fenóis/análise , Folhas de Planta/química , Polifenóis/análise , Proantocianidinas/análise , Ácido Quínico/análogos & derivados , Ácido Quínico/análise , Espectrometria de Massas por Ionização por Electrospray , Esfingolipídeos/análiseRESUMO
The chemical composition and biological activity of three parts (rind, flesh and seeds) of pumpkin fruits (Cucurbita pepo L.) cultivated in Egypt were studied. Chemical analysis of fibre, protein, ß-carotene, carbohydrates, minerals and fatty acids present in the rind, flesh, seeds and defatted seeds meal was conducted. Chemical, GC-MS and biological assays of organic extracts of the main fruit parts, rind and flesh established their unique constituents. Chromatographic purification of the extracts afforded triglyceride fatty acid mixture (1), tetrahydro-thiophene (2), linoleic acid (3), calotropoleanly ester (4), cholesterol (5) and 13(18)-oleanen-3-ol (6). GC-MS analysis of the extract's unpolar fraction revealed the existence of dodecane and tetradecane. Structures of the isolated compounds (1-6) were confirmed by NMR and EI-MS spectrometry. Antimicrobial, antiviral and antitumour activities of the fruit parts were discussed. The promising combined extract of rind and flesh was biologically studied for microbial and cytotoxic activities in comparison with the whole isolated components.