Publicação
Digested raspberries polyphenols for brain health: attenuation of neuroinflammation
| Resumo: | Microglia are the resident innate immune cells in the central nervous system (CNS), representing the first defense line of the neural parenchyma. However, its chronic activation is implicated in neurodegenerative disorders by the uncontrolled release of diverse molecular mediators such as inflammatory cytokines. Among all dietary phytochemicals, polyphenols are the major anti-inflammatory molecules provided by some plants. As example, raspberries are an enriched natural source of polyphenols such as ellagic acid, flavanols; and phenolic acids. However, digestion strongly modifies the structure of polyphenols, producing metabolites with different bioactivities. Thus, it is imperative the study of digested polyphenols for a better elucidation about their effects. The main goal of this study was to evaluate the bioactivity of raspberry polyphenols as neuroinflammatory attenuators. The fractions studied were composed by polyphenols that are bioaccessible to blood serum, obtained from in vitro digestion of five different quasi-isogenic raspberries. Furthermore, N9 murine microglial cell line was implemented as model of neuroinflammation and the range of non-cytotoxic concentrations of each fraction was determined. Then, the neuroinflammatory attenuation induced by each digested fraction in LPS-stimulated microglia was evaluated and compared. As result, some of the fractions attenuated microglial pro-inflammatory activation, significantly decreasing the expression of membrane protein CD-40 (marker of microglial activation) and the production of the pro-inflammatory markers, nitric oxide (NO), tumor necrosis factor-α (TNF-α) and intracellular superoxide (O2•-). Additionally, a yeast model of inflammation was used as a mechanistic tool to elucidate the molecular mechanisms underlying the anti-inflammatory activity of the digested raspberry fractions. The results showed that these compounds inhibit the yeast Crz1/calcineurin pathway, which is homologous to the mammalian nuclear factor of activated T-cells (NFAT)/calcineurin, suggesting that they may prevent microglial neuroinflammation through this pathway. |
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| Autores principais: | Garcia, Gonçalo Filipe Rodrigues, 1990- |
| Assunto: | Neuroinflamação Polifenois Microglia Teses de mestrado - 2014 |
| Ano: | 2014 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Microglia are the resident innate immune cells in the central nervous system (CNS), representing the first defense line of the neural parenchyma. However, its chronic activation is implicated in neurodegenerative disorders by the uncontrolled release of diverse molecular mediators such as inflammatory cytokines. Among all dietary phytochemicals, polyphenols are the major anti-inflammatory molecules provided by some plants. As example, raspberries are an enriched natural source of polyphenols such as ellagic acid, flavanols; and phenolic acids. However, digestion strongly modifies the structure of polyphenols, producing metabolites with different bioactivities. Thus, it is imperative the study of digested polyphenols for a better elucidation about their effects. The main goal of this study was to evaluate the bioactivity of raspberry polyphenols as neuroinflammatory attenuators. The fractions studied were composed by polyphenols that are bioaccessible to blood serum, obtained from in vitro digestion of five different quasi-isogenic raspberries. Furthermore, N9 murine microglial cell line was implemented as model of neuroinflammation and the range of non-cytotoxic concentrations of each fraction was determined. Then, the neuroinflammatory attenuation induced by each digested fraction in LPS-stimulated microglia was evaluated and compared. As result, some of the fractions attenuated microglial pro-inflammatory activation, significantly decreasing the expression of membrane protein CD-40 (marker of microglial activation) and the production of the pro-inflammatory markers, nitric oxide (NO), tumor necrosis factor-α (TNF-α) and intracellular superoxide (O2•-). Additionally, a yeast model of inflammation was used as a mechanistic tool to elucidate the molecular mechanisms underlying the anti-inflammatory activity of the digested raspberry fractions. The results showed that these compounds inhibit the yeast Crz1/calcineurin pathway, which is homologous to the mammalian nuclear factor of activated T-cells (NFAT)/calcineurin, suggesting that they may prevent microglial neuroinflammation through this pathway. |
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