Articles producció científica> Bioquímica i Biotecnologia

5-(Hydroxyphenyl)-gamma-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models

  • Identification data

    Identifier: imarina:6012531
    Authors:
    Angelino, DonatoCarregosa, DiogoDomenech-Coca, CristinaSavi, MoniaFigueira, InesBrindani, NicolettaJang, SaebyeolLakshman, SuklaMolokin, AlekseyUrban, Joseph E., Jr.Davis, Cindy D.Brito, Maria AlexandraKim, Kwang SikBrighenti, FurioCurti, ClaudioBlade, Cintadel Bas, Josep M.Stilli, DonatellaSolano-Aguilar, Gloria, Idos Santos, Claudia Nunesdel Rio, DanieleMena, Pedro
    Abstract:
    Phenolic compounds have been recognized as promising compounds for the prevention of chronic diseases, including neurodegenerative ones. However, phenolics like flavan-3-ols (F3O) are poorly absorbed along the gastrointestinal tract and structurally rearranged by gut microbiota, yielding smaller and more polar metabolites like phenyl-gamma-valerolactones, phenylvaleric acids and their conjugates. The present work investigated the ability of F3O-derived metabolites to cross the blood-brain barrier (BBB), by linking five experimental models with increasing realism. First, an in silico study examined the physical-chemical characteristics of F3O metabolites to predict those most likely to cross the BBB. Some of these metabolites were then tested at physiological concentrations to cross the luminal and abluminal membranes of brain microvascular endothelial cells, cultured in vitro. Finally, three different in vivo studies in rats injected with pure 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone, and rats and pigs fed grapes or a F3O-rich cocoa extract, respectively, confirmed the presence of 5-(hydroxyphenyl)-gamma-valerolactone-sulfate (3',4' isomer) in the brain. This work highlighted, with different experimental models, the BBB permeability of one of the main F3O-derived metabolites. It may support the neuroprotective effects of phenolic-rich foods in the frame of the gut-brain axis.
  • Others:

    Author, as appears in the article.: Angelino, Donato; Carregosa, Diogo; Domenech-Coca, Cristina; Savi, Monia; Figueira, Ines; Brindani, Nicoletta; Jang, Saebyeol; Lakshman, Sukla; Molokin, Aleksey; Urban, Joseph E., Jr.; Davis, Cindy D.; Brito, Maria Alexandra; Kim, Kwang Sik; Brighenti, Furio; Curti, Claudio; Blade, Cinta; del Bas, Josep M.; Stilli, Donatella; Solano-Aguilar, Gloria, I; dos Santos, Claudia Nunes; del Rio, Daniele; Mena, Pedro;
    Department: Bioquímica i Biotecnologia
    URV's Author/s: BLADÉ SEGARRA, MARIA CINTA / Del Bas Prior, José María / DOMENECH COCA, CRISTINA
    Keywords: Vitis Valerolactone Swine Sulfates Rats Proanthocyanidin Prediction Polyphenols Plant extracts Permeability Pentanoic acids Neurodegenerative disease Models, theoretical Metabolites Lactones Humans Gut Flavonoids Flavan-3-ol Endothelial cells Drug solubility Cognitive decline Cocoa Catechin Cacao Brain Blood-brain barrier Blood brain barrier Animals proanthocyanidin polyphenols permeability neurodegenerative disease metabolites gut flavan-3-ol catechin blood brain barrier
    Abstract: Phenolic compounds have been recognized as promising compounds for the prevention of chronic diseases, including neurodegenerative ones. However, phenolics like flavan-3-ols (F3O) are poorly absorbed along the gastrointestinal tract and structurally rearranged by gut microbiota, yielding smaller and more polar metabolites like phenyl-gamma-valerolactones, phenylvaleric acids and their conjugates. The present work investigated the ability of F3O-derived metabolites to cross the blood-brain barrier (BBB), by linking five experimental models with increasing realism. First, an in silico study examined the physical-chemical characteristics of F3O metabolites to predict those most likely to cross the BBB. Some of these metabolites were then tested at physiological concentrations to cross the luminal and abluminal membranes of brain microvascular endothelial cells, cultured in vitro. Finally, three different in vivo studies in rats injected with pure 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone, and rats and pigs fed grapes or a F3O-rich cocoa extract, respectively, confirmed the presence of 5-(hydroxyphenyl)-gamma-valerolactone-sulfate (3',4' isomer) in the brain. This work highlighted, with different experimental models, the BBB permeability of one of the main F3O-derived metabolites. It may support the neuroprotective effects of phenolic-rich foods in the frame of the gut-brain axis.
    Thematic Areas: Zootecnia / recursos pesqueiros Saúde coletiva Química Psicología Planejamento urbano e regional / demografia Nutrition and dietetics Nutrition & dietetics Nutrição Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar Food science Farmacia Engenharias iv Engenharias ii Enfermagem Educação física Economia Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências agrárias i Ciência de alimentos Biotecnología
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 20726643
    Author's mail: josepm.delbas@urv.cat
    Record's date: 2024-06-28
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.mdpi.com/2072-6643/11/11/2678
    Papper original source: Nutrients. 11 (11): E2678-
    APA: Angelino, Donato; Carregosa, Diogo; Domenech-Coca, Cristina; Savi, Monia; Figueira, Ines; Brindani, Nicoletta; Jang, Saebyeol; Lakshman, Sukla; Moloki (2019). 5-(Hydroxyphenyl)-gamma-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models. Nutrients, 11(11), E2678-. DOI: 10.3390/nu11112678
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Article's DOI: 10.3390/nu11112678
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2019
    Publication Type: Journal Publications
  • Keywords:

    Food Science,Nutrition & Dietetics,Nutrition and Dietetics
    Vitis
    Valerolactone
    Swine
    Sulfates
    Rats
    Proanthocyanidin
    Prediction
    Polyphenols
    Plant extracts
    Permeability
    Pentanoic acids
    Neurodegenerative disease
    Models, theoretical
    Metabolites
    Lactones
    Humans
    Gut
    Flavonoids
    Flavan-3-ol
    Endothelial cells
    Drug solubility
    Cognitive decline
    Cocoa
    Catechin
    Cacao
    Brain
    Blood-brain barrier
    Blood brain barrier
    Animals
    proanthocyanidin
    polyphenols
    permeability
    neurodegenerative disease
    metabolites
    gut
    flavan-3-ol
    catechin
    blood brain barrier
    Zootecnia / recursos pesqueiros
    Saúde coletiva
    Química
    Psicología
    Planejamento urbano e regional / demografia
    Nutrition and dietetics
    Nutrition & dietetics
    Nutrição
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Interdisciplinar
    Food science
    Farmacia
    Engenharias iv
    Engenharias ii
    Enfermagem
    Educação física
    Economia
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências agrárias i
    Ciência de alimentos
    Biotecnología
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