RESUMEN
Apples represent a significant source of dietary phenolic compounds with evidenced anti-inflammatory and immunomodulatory activities. Nevertheless, the effect of the whole apple matrix on human macrophages is unknown. In this context, our study attempts to evaluate the effect of apple-derived phenolic compounds-rich extracts (pulp, peel and leaf) on IL-1ß production in THP-1-differentiated macrophages and derived metabolic alterations through untargeted metabolomics. Our results have showed that apple pulp treatment inhibited the release of the pro-inflammatory cytokine IL-1ß induced by LPS in THP-1 macrophages by ELISA analysis. Metabolomics demonstrate that different proportions of phenolic compounds led to differential alterations in the metabolism of THP-1 macrophages. Indeed, apple extracts promoted alterations in lipid, carbohydrate, amino acid and vitamins as well as cofactors metabolism. Specifically, leaf extracts were characterized by alteration of galactose metabolism while the extracts derived from the fruit showed predominant alterations in lipids metabolism. All extracts mimicked the response observed under normal conditions in LPS-stimulated macrophages, inhibiting LPS response. Thus, the phenolic enriched extracts from apples will be a good source of natural compounds with a beneficial effect against inflammation, and they may be applied as a food supplement and/or functional ingredient for the treatment of inflammatory diseases.
Asunto(s)
Malus , Humanos , Lipopolisacáridos/farmacología , Macrófagos , Metabolómica , Fenoles/metabolismo , Fenoles/farmacología , Extractos Vegetales/químicaRESUMEN
The effect of three dietary tannins (procyanidin B3, B6, and T2) on the bioavailability of the 32-mer gliadin-derived immunogenic peptide was evaluated. An enterocyte-like Caco-2 cell line was used to mimic the epithelial transport of the 32-mer peptide, which was modeled by kinetic parameters with a mass spectrometry approach. The hydrolysis pattern on the enterocytes was analyzed, and the released peptides were quantified during the assay. The transport flux was dose-dependent. Along with procyanidin T2 and B6, procyanidin B3 promoted a significant inhibition mainly at the 100 µM peptide concentration. The hydrolysis efficiency was affected by procyanidins, while the cleavage pattern was suggested to be promoted by brush-border membranes at the apical compartment. The ability of procyanidins to molecularly bind to immunogenic peptides able to induce an adaptive response arose as a mechanism able to modulate their bioavailability, bioaccesibility, and further T CD4+ cell activation and expansion in a celiac disease (CD) model.
Asunto(s)
Enfermedad Celíaca , Vitis , Células CACO-2 , Enfermedad Celíaca/tratamiento farmacológico , Gliadina , Humanos , Péptidos , PolifenolesRESUMEN
Dihydrochalcones, phlorizin (PZ) and its aglycone phloretin (PT), have evidenced immunomodulatory effects through several mechanisms. However, the differential metabolic signatures that lead to these properties are largely unknown. Since macrophages play an important role in the immune response, our study aimed to characterise human THP-1 macrophages under PZ and PT exposure. A multiplatform-based untargeted metabolomics approach was used to reveal metabolites associated with the anti-inflammatory mechanisms triggered by the dihydrochalcones in LPS-stimulated macrophages, for the first time. Results showed differential phenotypic response in macrophages for all treatments. Dihydrochalcone treatment in LPS-stimulated macrophages mimics the response under normal conditions, suggesting inhibition of LPS response. Antagonistic effects of dihydrochalcones against LPS was mainly observed in glycerophospholipid and sphingolipid metabolism besides promoting amino acid biosynthesis. Moreover, PT showed greater metabolic activity than PZ. Overall, the findings of this study yielded knowledge about the mechanisms of action PZ and PT at metabolic level in modulating inflammatory response in human cells.
Asunto(s)
Factores Inmunológicos , Macrófagos/inmunología , Metabolómica , Floretina , Florizina , Humanos , Factores Inmunológicos/farmacocinética , Factores Inmunológicos/farmacología , Floretina/farmacocinética , Floretina/farmacología , Florizina/farmacocinética , Florizina/farmacología , Células THP-1RESUMEN
BACKGROUND: Interest in protein-phenol interactions in biological systems has grown substantially in recent decades. METHODS: The interest has focused largely on food systems in response to reports on the prominent roles of phenolic compounds in nutrition and health. RESULTS: Phenolic compounds can have both favourable and adverse nutritional effects. Polyphenols are widely known for their antioxidant, anti-inflammatory, anticancer and antiaging properties; however, they have also been ascribed anti-nutritional effects resulting from interactions with some proteins and enzymes. Interactions between proteins and polyphenols can additionally influence food quality by altering some physical-chemical and sensory properties of foods. These effects may be useful to develop new products in food science and technology provided the nature of physical-chemical interactions between proteins and phenols is accurately elucidated. In this paper, we review the different possible modes of interaction between selected food proteins and phenolic compounds. CONCLUSION: Existing knowledge on the mechanisms behind polyphenol-protein reactions, the structures of the resulting products and their potential uses is reviewed.
Asunto(s)
Antiinflamatorios/metabolismo , Antioxidantes/metabolismo , Calidad de los Alimentos , Proteínas de Vegetales Comestibles/metabolismo , Polifenoles/metabolismo , Animales , Antiinflamatorios/administración & dosificación , Antioxidantes/administración & dosificación , Humanos , Resonancia Magnética Nuclear Biomolecular/métodos , Proteínas de Vegetales Comestibles/administración & dosificación , Polifenoles/administración & dosificación , Unión Proteica/fisiologíaRESUMEN
Tannins have the ability to complex and precipitate proteins, being particularly reactive towards the proline-rich ones. The main structural feature of the wheat peptides responsible for the onset of Celiac Disease (CD) is their high content in proline residues. The aim of this work was to characterize the binding between a common food tannin (procyanidin B3) and different wheat-derived peptidic fractions. For this, seven peptide mixtures were obtained after in vitro digestion of a wheat gliadins crude extract and further characterized by LC-ESI-MS/MS. Several soluble B3-peptide complexes were identified by ESI-MS. The peptides involved in complex formation varied in terms of their size and diversity in CD epitopes. Although binding selectivity of procyanidin B3 towards peptides containing CD epitopes was not found, the major complexes contained or could contain immunoreactive peptides. This study highlights the potential beneficial effects of food polyphenols as a nutritional approach in the modulation of CD.
Asunto(s)
Biflavonoides/química , Catequina/química , Enfermedad Celíaca/metabolismo , Péptidos/química , Proantocianidinas/química , Triticum/metabolismo , Biflavonoides/metabolismo , Catequina/metabolismo , Humanos , Péptidos/metabolismo , Proantocianidinas/metabolismo , Espectrometría de Masas en Tándem , Triticum/químicaRESUMEN
Several factors could influence the tannin-protein interaction such as the human salivary protein profile, the tannin tested, and the tannin/protein ratio. The goal of this study aims to study the effect of different salivas (A, B, and C) and different tannin concentrations (0.5 and 1 mg/mL) on the interaction process as well as the complex's stability over time. This study is focused on the identification of new procyanidin B3-human salivary protein complexes. Thus, 48 major B3-human salivary protein aggregates were identified regardless of the saliva and tannin concentration tested. A higher number of aggregates was found at lower tannin concentration. Moreover, the number of protein moieties involved in the aggregation process was higher when the tannin concentration was also higher. The selectivity of the different groups of proteins to bind tannin was also confirmed. It was also verified that the B3-human salivary protein complexes formed evolved over time.