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: Valerolactone Rats Proanthocyanidin Prediction Polyphenols Permeability Neurodegenerative disease Metabolites Gut Flavan-3-ol Drug solubility Cognitive decline Cocoa Catechin Blood brain barrier 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: 2023-02-18

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.mdpi.com/2072-6643/11/11/2678

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Nutrients. 11 (11):

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), -. DOI: 10.3390/nu11112678

Article's DOI: 10.3390/nu11112678

Entity: Universitat Rovira i Virgili

Journal publication year: 2019

Publication Type: Journal Publications