RESUMO
The accumulation of amyloid-ß protein (Aß) in brain is linked to the early pathogenesis of Alzheimer's disease (AD). We previously reported that neuron-derived exosomes promote Aß clearance in the brains of amyloid precursor protein transgenic mice and that exosome production is modulated by ceramide metabolism. Here, we demonstrate that plant ceramides derived from Amorphophallus konjac, as well as animal-derived ceramides, enhanced production of extracellular vesicles (EVs) in neuronal cultures. Oral administration of plant glucosylceramide (GlcCer) to APP overexpressing mice markedly reduced Aß levels and plaque burdens and improved cognition in a Y-maze learning task. Moreover, there were substantial increases in the neuronal marker NCAM-1, L1CAM, and Aß in EVs isolated from serum and brain tissues of the GlcCer-treated AD model mice. Our data showing that plant ceramides prevent Aß accumulation by promoting EVs-dependent Aß clearance in vitro and in vivo provide evidence for a protective role of plant ceramides in AD. Plant ceramides might thus be used as functional food materials to ameliorate AD pathology.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Amorphophallus/química , Peptídeos beta-Amiloides/genética , Vesículas Extracelulares/metabolismo , Glucosilceramidas/efeitos adversos , Administração Oral , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/citologia , Antígeno CD56/metabolismo , Modelos Animais de Doenças , Glucosilceramidas/química , Glucosilceramidas/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Extratos Vegetais/químicaRESUMO
Background: The aim of this double-blind randomized cross-over trial was to evaluate the effect of oral intake of glucosylceramide extracted from pineapple on oral moisture and xerostomia symptoms. Methods: Sixteen participants who had xerostomia symptoms were randomly allocated into two groups. One group received, as test samples, tablets containing glucosylceramide extracted from pineapple (GCP) followed by placebo tablets. The other group received the test samples in the reverse order. Participants were instructed to take tablets of the first test sample once a day (after breakfast) for two consecutive weeks. Then, after a washout period of four weeks, participants were instructed to take the other test sample for two consecutive weeks. The oral moisture level of the lingual mucosa, xerostomia symptoms, and the number of fungiform papillae was evaluated. Results: The oral moisture significantly increased, and the visual analog scale (VAS) of "How is the dryness of your mouth?" significantly improved after GCP tablets intake and not after placebo tablets intake. The number of fungiform papillae was not significantly different following the intake of GCP tablets or placebo tablets. Conclusion: Results suggested that oral intake of GCP may improve the moisture level and xerostomia symptoms.