Data suggest that intestinal carotenoid absorption is a facilitated process. The present study was conducted to determine whether carotenoids and cholesterol share common pathways (transporters) for their intestinal absorption. Differentiated Caco-2 cells on membranes were incubated (16 h) with a carotenoid (1 micromol/L) with or without ezetimibe (EZ; Zetia, an inhibitor of cholesterol transport), and with or without antibodies against the receptors, cluster determinant 36 (CD36) and scavenger receptor class B, type I (SR-BI). Carotenoid transport in Caco-2 cells (cellular uptake + secretion) was decreased by EZ (10 mg/L) as follows: beta-carotene approximately alpha-carotene (50% inhibition) >> beta-cryptoxanthin approximately lycopene (20%) >> lutein:zeaxanthin (1:1) (7%). EZ reduced cholesterol transport by 31%, but not retinol transport. beta-Carotene transport was also inhibited by anti-SR-BI, but not by anti-CD36. The inhibitory effects of EZ and anti-SR-BI on beta-carotene transport were additive, indicating that they may have different targets. Finally, differentiated Caco-2 cells treated with EZ showed a significant decrease in mRNA expression for the surface receptors SR-BI, Niemann-Pick type C1 Like 1 protein (NPC1L1), and ATP-binding cassette transporter, subfamily A (ABCA1) and for the nuclear receptors retinoid acid receptor (RAR)gamma, sterol-regulatory element binding proteins (SREBP)-1 and -2, and liver X receptor (LXR)beta as assessed by real-time PCR analysis. The data indicate that 1) EZ is an inhibitor of carotenoid transport, an effect that decreases with increasing polarity of the carotenoid molecule, 2) SR-BI is involved in carotenoid transport, and 3) EZ may act, not only by interacting physically with cholesterol transporters as previously suggested, but also by downregulating expression of these proteins. The cellular uptake and efflux of carotenoids, like that of cholesterol, likely involve more than one transporter.

Inflammatory bowel diseases (IBD) arise from multiple causes, including environmental factors, gut microflora, immunity, and genetic predispositions. In the course of IBD, immune homeostasis and intestinal mucosa barrier integrity are impaired. Among natural preventive treatments that have been identified to date, polyphenols appear as promising candidates. They have been shown to protect against several diseases, including cardiovascular diseases and cancers, and they have anti-inflammatory properties in non-intestinal models. This paper will review the literature that has described to date some effects of polyphenols on intestinal inflammation. Studies, conducted using in vivo and in vitro models, provide evidence that pure polyphenolic compounds and natural polyphenolic plant extracts can modulate intestinal inflammation.

Recent studies support beneficial effects of polyphenols in various chronic inflammatory diseases, for example, the inflammatory bowel diseases. Inhibition of NF-kB activation by polyphenols could explain part of their anti-inflammatory properties, but few data are available on the intestine. The purpose of the present study was thus to investigate the effects of some polyphenols on NF-kB activation using human intestinal Caco-2 cells. Effects of standard polyphenols (50 mmol/l) were studied on different cellular events associated with NF-kB activation: (i) NF-kB activity using cells transiently transfected with a NF-kB -luciferase construct and stimulated by inflammatory agents (IL-1b, TNF-a or lipopolysaccharides (LPS)); (ii) phosphorylation of the inhibitor of kB (IkB-a) analysed by Western blot; (iii) secretion of IL-8 quantified by ELISA assay. Results showed that chrysin and ellagic acid inhibited NF-kB activity, whereas genistein and resveratrol increased it. These effects were independent of the nature of the inducer, indicating that polyphenols may modulate NF-kB activation by acting on a common event to the cytokine-and LPSmediated cascades. Chrysin strongly reduced (2·5-fold) IL-1b-induced IkB-a phosphorylation, whereas ellagic acid increased it (1·7-fold). Ellagic acid, genistein and epigallocatechin gallate reduced (4-to 8-fold) IL-1b-induced IL-8 secretion, while resveratrol promoted (1·7-fold) the secretion. Chrysin also diminished IL-8 secretion by 1·6-fold (but P. 0·05). The data indicate that polyphenols can modulate the NF-kB activation pathway in the intestine. Chrysin could block NF-kB activation via the inhibition of IkB-a phosphorylation. The other molecular targets of the active polyphenols are still to be identified.

The purpose of this study was to investigate the mechanisms by which carotenoids [xanthophylls vs. bcarotene (b-C)] are taken up by retinal pigment epithelial (RPE) cells. The human RPE cell line, ARPE-19, was used. When ARPE-19 cells were fully differentiated (7-9 weeks), the xanthophylls lutein (LUT) and zeaxanthin (ZEA) were taken up by cells to an extent 2-fold higher than b-C (P , 0.05). At 9 weeks, cellular uptakes were 1.6, 2.5, and 3.2%, respectively, for b-C, LUT, and ZEA. Similar extents were observed when carotenoids were delivered in either Tween 40 or "chylomicrons" produced by Caco-2 cells. Differentiated ARPE-19 cells did not exhibit any detectable b-C 15,15′-oxygenase activity or convert exogenous b-C into vitamin A. When using specific antibodies against the lipid transporters cluster determinant 36 (CD36) and scavenger receptor class B type I (SR-BI), cellular uptake of b-C and ZEA were significantly decreased (40-60%) with anti-SR-BI but not with anti-CD36. Small interfering RNA transfection for SR-BI led to marked knockdown of SR-BI protein expression (?90%), which resulted in decreased b-C and ZEA uptakes by 51% and 87%, respectively. Thus, the present data show that RPE cells preferentially take up xanthophylls versus the carotene by a process that appears to be entirely SR-BI-dependent for ZEA and partly so for b-C. This mechanism may explain, in part, the preferential accumulation of xanthophylls in the macula of the retina.-During, A., S. Doraiswamy, and E. H. Harrison. Xanthophylls are preferentially taken up compared with b-carotene by retinal cells via a SRBI-dependent mechanism.