title: Bioaccessible (poly)phenol metabolites from raspberry protect neural cells from oxidative stress and attenuate microglia activation.
abstract: Neuroinflammation is an integral part of the neurodegeneration process inherent to several aging dysfunctions. Within the central nervous system, microglia are the effective immune cells, responsible for neuroinflammatory responses. In this study, raspberries were subjected to in vitro digestion simulation to obtain the components that result from the gastrointestinal (GI) conditions, which would be bioaccessible and available for blood uptake. Both the original raspberry extract and the gastrointestinal bioaccessible (GIB) fraction protected neuronal and microglia cells against H2O2-induced oxidative stress and lipopolysaccharide (LPS)-induced inflammation, at low concentrations. Furthermore, this neuroprotective capacity was independent of intracellular ROS scavenging mechanisms. We show for the first time that raspberry metabolites present in the GIB fraction significantly inhibited microglial pro-inflammatory activation by LPS, through the inhibition of Iba1 expression, TNF-α release and NO production. Altogether, this study reveals that raspberry polyphenols may present a dietary route to the retardation or amelioration of neurodegenerative-related dysfunctions.
authors.affiliation: iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal.
authors.forename: Gonçalo
authors.initials: G
authors.lastname: Garcia
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Nanni
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Figueira
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Ines
authors.initials: I
authors.lastname: Ivanov
authors.affiliation: Enhancing Crop Productivity and Utilisation Theme, The James Hutton Institute, Dundee DD2 5DA, Scotland, United Kingdom.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: McDougall
authors.affiliation: Enhancing Crop Productivity and Utilisation Theme, The James Hutton Institute, Dundee DD2 5DA, Scotland, United Kingdom; School of Life Sciences, Heriot-Watt University, Edinburgh EH14 4AS, Scotland, United Kingdom.
authors.forename: Derek
authors.initials: D
authors.lastname: Stewart
authors.affiliation: Departamento de Botânica e Engenharia Biológica, Instituto Superior de Agronomia, Universidade Técnica de Lisboa, Tapada da Ajuda, 1349-017 Lisboa, Portugal.
authors.forename: Ricardo B
authors.initials: RB
authors.lastname: Ferreira
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal; Escola Superior Agrária, Instituto Politécnico de Santarém, Qta do Galinheiro, Santarém, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Pinto
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Rui F M
authors.initials: RF
authors.lastname: Silva
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. Electronic address: dbrites@ff.ulisboa.pt.
authors.forename: Dora
authors.initials: D
authors.lastname: Brites
authors.affiliation: iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal. Electronic address: csantos@itqb.unl.pt.
authors.forename: Cláudia N
authors.initials: CN
authors.lastname: Santos
mesh_terms: D006861:Hydrogen Peroxide / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D019800:Phenol / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology; D065856:Rubus; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D010936:Plant Extracts; D059808:Polyphenols; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019800:Phenol; D006861:Hydrogen Peroxide
keywords: Bioaccessibility; Neuroinflammation; Neuroprotective mechanisms; Oxidative stress; Polyphenols; Raspberry