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      Cytoprotective Effects of Natural Highly Bio-Available Vegetable Derivatives on Human-Derived Retinal Cells

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          Abstract

          Retinal pigment epithelial cells are crucial for retina maintenance, making their cytoprotection an excellent way to prevent or slow down retinal degeneration. In addition, oxidative stress, inflammation, apoptosis, neovascularization, and/or autophagy are key pathways involved in degenerative mechanisms. Therefore, here we studied the effects of curcumin, lutein, and/or resveratrol on human retinal pigment epithelial cells (ARPE-19). Cells were incubated with individual or combined agent(s) before induction of (a) H 2O 2-induced oxidative stress, (b) staurosporin-induced apoptosis, (c) CoCl 2-induced hypoxia, or (d) a LED-autophagy perturbator. Metabolic activity, cellular survival, caspase 3/7 activity (casp3/7), cell morphology, VEGF levels, and autophagy process were assessed. H 2O 2 provoked a reduction in cell survival, whereas curcumin reduced metabolic activity which was not associated with cell death. Cell death induced by H 2O 2 was significantly reduced after pre-treatment with curcumin and lutein, but not resveratrol. Staurosporin increased caspase-3/7 activity (689%) and decreased cell survival by 32%. Curcumin or lutein protected cells from death induced by staurosporin. Curcumin, lutein, and resveratrol were ineffective on the increase of caspase 3/7 induced by staurosporin. Pre-treatment with curcumin or lutein prevented LED-induced blockage of autophagy flux. Basal-VEGF release was significantly reduced by lutein. Therefore, lutein and curcumin showed beneficial protective effects on human-derived retinal cells against several insults.

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          High absorption but very low bioavailability of oral resveratrol in humans.

          The dietary polyphenol resveratrol has been shown to have chemopreventive activity against cardiovascular disease and a variety of cancers in model systems, but it is not clear whether the drug reaches the proposed sites of action in vivo after oral ingestion, especially in humans. In this study, we examined the absorption, bioavailability, and metabolism of 14C-resveratrol after oral and i.v. doses in six human volunteers. The absorption of a dietary relevant 25-mg oral dose was at least 70%, with peak plasma levels of resveratrol and metabolites of 491 +/- 90 ng/ml (about 2 microM) and a plasma half-life of 9.2 +/- 0.6 h. However, only trace amounts of unchanged resveratrol (<5 ng/ml) could be detected in plasma. Most of the oral dose was recovered in urine, and liquid chromatography/mass spectrometry analysis identified three metabolic pathways, i.e., sulfate and glucuronic acid conjugation of the phenolic groups and, interestingly, hydrogenation of the aliphatic double bond, the latter likely produced by the intestinal microflora. Extremely rapid sulfate conjugation by the intestine/liver appears to be the rate-limiting step in resveratrol's bioavailability. Although the systemic bioavailability of resveratrol is very low, accumulation of resveratrol in epithelial cells along the aerodigestive tract and potentially active resveratrol metabolites may still produce cancer-preventive and other effects.
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            Old, new and emerging functions of caspases.

            Caspases are proteases with a well-defined role in apoptosis. However, increasing evidence indicates multiple functions of caspases outside apoptosis. Caspase-1 and caspase-11 have roles in inflammation and mediating inflammatory cell death by pyroptosis. Similarly, caspase-8 has dual role in cell death, mediating both receptor-mediated apoptosis and in its absence, necroptosis. Caspase-8 also functions in maintenance and homeostasis of the adult T-cell population. Caspase-3 has important roles in tissue differentiation, regeneration and neural development in ways that are distinct and do not involve any apoptotic activity. Several other caspases have demonstrated anti-tumor roles. Notable among them are caspase-2, -8 and -14. However, increased caspase-2 and -8 expression in certain types of tumor has also been linked to promoting tumorigenesis. Increased levels of caspase-3 in tumor cells causes apoptosis and secretion of paracrine factors that promotes compensatory proliferation in surrounding normal tissues, tumor cell repopulation and presents a barrier for effective therapeutic strategies. Besides this caspase-2 has emerged as a unique caspase with potential roles in maintaining genomic stability, metabolism, autophagy and aging. The present review focuses on some of these less studied and emerging functions of mammalian caspases.
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              Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research.

              Curcuma longa (turmeric) has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. Turmeric constituents include the three curcuminoids: curcumin (diferuloylmethane; the primary constituent and the one responsible for its vibrant yellow color), demethoxycurcumin, and bisdemethoxycurcumin, as well as volatile oils (tumerone, atlantone, and zingiberone), sugars, proteins, and resins. While numerous pharmacological activities, including antioxidant and antimicrobial properties, have been attributed to curcumin, this article focuses on curcumin's anti-inflammatory properties and its use for inflammatory conditions. Curcumin's effect on cancer (from an anti-inflammatory perspective) will also be discussed; however, an exhaustive review of its many anticancer mechanisms is outside the scope of this article. Research has shown curcumin to be a highly pleiotropic molecule capable of interacting with numerous molecular targets involved in inflammation. Based on early cell culture and animal research, clinical trials indicate curcumin may have potential as a therapeutic agent in diseases such as inflammatory bowel disease, pancreatitis, arthritis, and chronic anterior uveitis, as well as certain types of cancer. Because of curcumin's rapid plasma clearance and conjugation, its therapeutic usefulness has been somewhat limited, leading researchers to investigate the benefits of complexing curcumin with other substances to increase systemic bioavailability. Numerous in-progress clinical trials should provide an even deeper understanding of the mechanisms and therapeutic potential of curcumin.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                24 March 2020
                March 2020
                : 12
                : 3
                : 879
                Affiliations
                [1 ]UMR1107 NeuroDol, Université Clermont-Auvergne, TSA 50400, 28 Place Henri Dunant, 63000 Clermont-Ferrand, France; il.munia@ 123456gmail.com (I.M.); laurent.gafray@ 123456laposte.net (L.G.); Nathalie.JACQUEMOT@ 123456uca.fr (N.J.); Christine.CERCY@ 123456uca.fr (C.C.); rbo.khaoula@ 123456live.fr (K.R.B.O.)
                [2 ]Centre des Sciences du Goût et de l’Alimentation, AgroSup Dijon, CNRS, INRAE, University of Bourgogne Franche-Comté, Eye and Nutrition Research Group, F-21000 Dijon, France; marie-agnes.bringer@ 123456inra.fr (M.-A.B.); lil.proukhnitzky@ 123456gmail.com (L.P.)
                [3 ]Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, 75012 Paris, France; pablogol@ 123456aol.com (P.G.); errera.mhelene@ 123456gmail.com (M.H.E.)
                Author notes
                [* ]Correspondence: isabelle.ranchon-cole@ 123456uca.fr ; Tel.: +33-473-17-79-80
                Author information
                https://orcid.org/0000-0002-7092-6744
                Article
                nutrients-12-00879
                10.3390/nu12030879
                7146218
                32214021
                ab96cea5-24ff-4964-bf4d-1a67f4a28aef
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 06 February 2020
                : 21 March 2020
                Categories
                Article

                Nutrition & Dietetics
                retina,damage,protection curcumin,resveratrol,lutein,antioxidant,apoptosis,autophagy
                Nutrition & Dietetics
                retina, damage, protection curcumin, resveratrol, lutein, antioxidant, apoptosis, autophagy

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