Next Article in Journal
Older Adults’ Awareness and Knowledge of Beans in Relation to Their Nutrient Content and Role in Chronic Disease Risk
Next Article in Special Issue
PipeNig®-FL, a Fluid Extract of Black Pepper (Piper Nigrum L.) with a High Standardized Content of Trans-β-Caryophyllene, Reduces Lipid Accumulation in 3T3-L1 Preadipocytes and Improves Glucose Uptake in C2C12 Myotubes
Previous Article in Journal
Nutritional Qualities of Commercial Meal Kit Subscription Services in Australia
Previous Article in Special Issue
Catechin and Procyanidin B2 Modulate the Expression of Tight Junction Proteins but Do Not Protect from Inflammation-Induced Changes in Permeability in Human Intestinal Cell Monolayers
Open AccessFeature PaperArticle

5-(Hydroxyphenyl)-γ-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

1
Human Nutrition Unit, Department of Veterinary Medicine, University of Parma, 43125 Parma, Italy
2
CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal
3
Unitat de Nutrició i Salut, Centre Tecnològic de Catalunya, Eurecat, 43204 Reus, Spain
4
Department of Biochemistry and Biotechnology, Nutrigenomics Research Group, Universitat Rovira i Virgili, 43007 Tarragona, Spain
5
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy
6
Instituto de Tecnologia Quı́mica e Biológica–António Xavier, Universidade Nova de Lisboa, EAN, 2781-901 Oeiras, Portugal
7
Human Nutrition Unit, Department of Food and Drug, University of Parma, 43125 Parma, Italy
8
Department of Food and Drug, University of Parma, 43125 Parma, Italy
9
U.S. Department of Agriculture, Northeast Area, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet Genomics and Immunology Laboratory, Beltsville, MD 20705, USA
10
Office of Dietary Supplements, National Institutes of Health, Bethesda, MD 20892, USA
11
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal
12
Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal
13
Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
14
Instituto de Biologia Experimental e Tecnológica, 2781-901 Oeiras, Portugal
15
School of Advanced Studies on Food and Nutrition, University of Parma, 43124 Parma, Italy
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(11), 2678; https://doi.org/10.3390/nu11112678
Received: 6 September 2019 / Revised: 23 October 2019 / Accepted: 24 October 2019 / Published: 5 November 2019
(This article belongs to the Special Issue Plant Food, Nutrition and Human Health)
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-γ-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)-γ-valerolactone, and rats and pigs fed grapes or a F3O-rich cocoa extract, respectively, confirmed the presence of 5-(hydroxyphenyl)-γ-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”. View Full-Text
Keywords: blood brain barrier; catechin; flavan-3-ol; gut; metabolites; permeability; proanthocyanidin; polyphenols; valerolactone; neurodegenerative disease blood brain barrier; catechin; flavan-3-ol; gut; metabolites; permeability; proanthocyanidin; polyphenols; valerolactone; neurodegenerative disease
Show Figures

Graphical abstract

MDPI and ACS Style

Angelino, D.; Carregosa, D.; Domenech-Coca, C.; Savi, M.; Figueira, I.; Brindani, N.; Jang, S.; Lakshman, S.; Molokin, A.; Urban, J.F., Jr.; Davis, C.D.; Brito, M.A.; Kim, K.S.; Brighenti, F.; Curti, C.; Bladé, C.; del Bas, J.M.; Stilli, D.; Solano-Aguilar, G.I.; Santos, C.N.; del Rio, D.; Mena, P. 5-(Hydroxyphenyl)-γ-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 2019, 11, 2678.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop