Bioavailability of the Polyphenols: Status and Controversies

The current interest in polyphenols has been driven primarily by epidemiological studies. However, to establish conclusive evidence for the effectiveness of dietary polyphenols in disease prevention, it is useful to better define the bioavailability of the polyphenols, so that their biological activity can be evaluated. The bioavailability appears to differ greatly among the various phenolic compounds, and the most abundant ones in our diet are not necessarily those that have the best bioavailability profile. In the present review, we focus on the factors influencing the bioavailability of the polyphenols. Moreover, a critical overview on the difficulties and the controversies of the studies on the bioavailability is discussed

Influence of deoxynivalenol on NF-kappa B activation and IL-8 secretion in human intestinal Caco-2 cells

Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. In human intestinal Caco-2 cells, DON activates the mitogen-activated protein kinases (MAPKs). We hypothesized a link between DON ingestion and intestinal inflammation, and used Caco-2 cells to assess the effects of DON, at plausible intestinal concentrations (250- 10,000 ng/ml), on inflammatory mediators acting downstream the MAPKs cascade i.e. activation of nuclear factor-kappa B (NF-kappa B) and interleukin-8 (IL-8) secretion. In addition, Caco-2 cells were co-exposed to pro-inflammatory stimuli in order to mimic an inflamed intestinal epithelium. Dose-dependent increases in NF-kappa B activity and IL-8 secretion were observed, reaching 1.4- and 7.6-fold, respectively using DON at 10 mu g/ml. Phosphorylation of inhibitor-kappa B (I kappa B) increased (1.6-fold) at DON levels <0.5 mu g/ml. Exposure of Caco-2 cells to pro-inflammatory agents, i.e. 25 ng/ml interleukin-1 beta, 100 ng/ml tumor necrosis factor-alpha or 10 mu g/ml lipopolysaccharides, activated NF-kappa B and increased IL-8 secretion. Synergistic interactions between these stimuli and DON were observed. These data show that DON induces NF-kappa B activation and IL-8 secretion dose-dependently in Caco-2 cells, and this effect was accentuated upon pro-inflammatory stimulation, suggesting DON exposure could cause or exacerbate intestinal inflammation. (C) 2008 Elsevier Ireland Ltd. All rights reserved

Gene expression profile in rat hippocampus with and without memory deficit

International audienceThe cholinergic neuronal system, through its projections to the hippocampus, plays an important role in learning and memory. The aim of the study was to identify genes and networks in rat hippocampus with and without memory deficit. Genome-scale screening was used to analyze gene expression changes in rats submitted or not to intraparenchymal injection of 192 IgG-saporin and trained in spatial/object novelty tasks. Results showed learning processes were associated with significant expression of genes that could be grouped into several clusters of similar expression profiles and that are involved in biological functions, namely lipid metabolism, signal transduction, protein metabolism and modification, and transcription regulation. Memory loss following hippocampal cholinergic deafferentation was associated with significant expression of genes that did not show similar cluster organization. Only one cluster of genes could be identified; it included genes that would be involved in tissue remodeling. More important, most of the genes significantly altered in lesioned rats were down-regulated. (c) 2010 Elsevier Inc. All rights reserved

Inflammatory parameters in Caco-2 cells: Effect of stimuli nature, concentration, combination and cell differentiation

Enterocytes regulate gut maintenance and defence by secreting and responding to inflammatory mediators and by modulating the intestinal epithelial permeability. In order to develop an in vitro model of the acute phase of intestinal inflammation, Caco-2 cells were exposed to the inflammatory mediators IL-1 beta, TNF-alpha, IFN-gamma and LPS, and the importance of several experimental parameters, i.e. cell differentiation, stimulus nature, concentration and combination on the inflammatory response was assessed by measuring the production of IL-6, IL-8, PGE-2 and NO and by evaluating the monolayer permeability. A maximal increase in IL-8, IL-6 and PGE-2 production and monolayer permeability was observed when using the cytokines simultaneously at their highest level, but this relied mainly on IL-1 beta. The effects of TNF-alpha on IL-8 and IL-6 or NO production were stronger upon combination with IL-1 beta or IFN-gamma, respectively, whereas cells were unaffected by the presence of LPS. Although NO production, induced by IFN-gamma-containing combinations, was observed only in differentiated cells, general inflammatory response was higher in proliferating cells. The use of a mixture of IL-1 beta, TNF-alpha and IFN-gamma thus accurately mimics intestinal inflammatory processes, but cell differentiation and stimuli combination are important parameters to take into account for in vitro studies on intestinal inflammation. (C) 2010 Published by Elsevier Ltd

Lycopene attenuates LPS-induced TNF-alpha secretion in macrophages and inflammatory markers in adipocytes exposed to macrophage-conditioned media

International audienceScope Adipose tissue is infiltrated by an increasing number of macrophages during the development of obesity. These immune cells are suspected to be a major source of TNF-a that interferes with adipocyte function. Because lycopene possesses anti-inflammatory properties, we hypothesize that lycopene could reduce the production of TNF-a by macrophages and thus interfere in the cross-talk between macrophages and adipocytes. Methods and results We demonstrated that physiological concentrations of lycopene were able to attenuate the lipopolysaccharide (LPS)-mediated induction of TNF-a in RAW 264.7 macrophages, at both the mRNA and protein levels. The molecular mechanism was studied. It appeared that the LPS-activation of both JNK and NF-?B signaling pathways was modulated by lycopene. The anti-inflammatory effects of lycopene on macrophages were accompanied by a decrease in LPS-stimulated macrophage migration in the presence of lycopene. Furthermore, lycopene decreased macrophage conditioned medium-induced proinflammatory cytokine, acute phase protein, and chemokine mRNA expression in 3T3-L1 adipocytes. Conclusion These data indicate that lycopene displayed an anti-inflammatory effect on macrophages that beneficially impacted adipocyte function. Thus, these results suggest that lycopene could block the vicious cycle that occurs between adipocytes and macrophages in adipose tissue during obesity

Elastic fibers and elastin receptor complex: Neuraminidase-1 takes the center stage

International audienceExtracellular matrix (ECM) has for a long time being considered as a simple architectural support for cells. It is now clear that ECM presents a fundamental influence on cells driving their phenotype and fate. This complex network is highly specialized and the different classes of macromolecules that comprise the ECM determine its biological functions. For instance, collagens are responsible for the tensile strength of tissues, proteoglycans and glycosaminoglycans are essential for hydration and resistance to compression, and glycoproteins such as laminins facilitate cell attachment. The largest structures of the ECM are the elastic fibers found in abundance in tissues suffering high mechanical constraints such as skin, lungs or arteries. These structures present a very complex composition whose core is composed of elastin surrounded by a microfibrils mantle. Elastogenesis is a tightly regulated process involving the sialidase activity of the Neuraminidase-1 (Neu-1) sub-unit of the Elastin Receptor Complex. Interestingly, Neu-1 subunit also serves as a sensor of elastin degradation via its ability to transmit elastin-derived peptides signaling. Finally, reports showing that neuraminidase activity is able to regulate TGF-β activation raises questions about a possible role for Neu-1 in elastic fibers remodeling. In this mini review, we develop the concept of the regulation of the whole life of elastic fibers through an original scope, the key role of Neu-1 sialidase enzymatic activity