BIOAVAILABILITY AND METABOLISM OF GRAPE TRANS-RESVERATROL ON CACO-2 CELLS

摘要

The consumption of polyphenol-rich diets is associated with a reduced risk of developing chronic diseases such as atherosclerosis, heart disease, cancer and diabetes (Manach et al., 2005). Grape derivatives, such as wine and grape juice are highly appreciated worldwide, and account for one of the most important sources of polyphenols in the human diet (Jackson, 2008). American varieties of V. labrusca L. are widely cultivated in North and South America and are a very relevant source of polyphenols inWestern diets (Nixdorf and Hermosin-Gutierrez, 2010). Many studies have reported that dietary intake of phenolic compounds is associated with health benefits related to cardiovascular function modulating various parameters such as, vascular and plateletfunction, blood pressure and the plasma lipid profile, as a result of improved resistance towards oxidative stress, inflammation, and endothelial dysfunction (Kemperman et al., 2013).The main phenolic compounds present in grape and grape juice are anthocyanins, mainly malvidin and cyanidin in their glucoside forms, flavonols (quercetin, myricetin, kaempferol) and flavan-3-ols (catechin and proanthocyanins), phenolic acids, trans-resveratrol and tannins (Jackson, 2008). The major grape polyphenols with clear impact on several cardiovascular markers are trans-resveratrol and quercetin. Several mechanistic studies with endothelial cells demonstrate the beneficial effect of trans-resveratrol and quercetin on angiogenesis, cell migration (Mojzis et al., 2008), markers for vasorelaxation and inflammatory factors (Duluc et al., 2013).trans-Resveratrol (RV) (trans-3,4,5-trihydroxystilbene) is a natural polyphenol present in grapes, red wine and berries that has been reported to exhibit beneficial effects against cardiovascular diseases (Jackson, 2008). In the human organism, during the course of absorption, polyphenols undergo extensive modification. Dietary polyphenols are conjugated in the intestinal cells and later in the liver by methylation, sulfation and glucuronidation (Pandey and Rizvi, 2009). The Caco-2 cell-monolayer comprises a well-established in vitro model for intestinal absorption and can generate useful information in order to predict in vivo mechanisms. Indeed, polyphenols undergo excessive metabolization by the intestinal microbiota and the gut epithelial cells, resulting in metabolites that are released into the bloodstream with potential to elicit health benefits on target tissues (Storniolo and Moreno, 2012). In order to investigate the metabolism of trans-resveratrol and the bioactive potential of this grape polyphenol, the cell conversion and transport of trans-resveratrol through Caco-2 cells for the detection of metabolites was evaluated. In addition, to verify RV bioactivity on a different target tissue, cellular reactivity to RV was evaluated on the human endothelial cell line EA.hy926, using the MTT and SRB protocols.