Resveratrol improves TNF-α-induced endothelial dysfunction in a coculture model of a Caco-2 with an endothelial cell line

Abstract

The bioactivity of trans-Resveratrol (RSV), an important wine polyphenol, and of its 53 metabolites was investigated in a more relevant setup comprising an in vitro co-culture cell 54 model that combines intestinal absorption and conjugation with changes in endothelial 55 function, which is primarily affected in cardiovascular diseases. Caco-2 and endothelial 56 EA.hy926 cells were grown in a co-culture and Caco-2 cells were treated with RSV, in the 57 co-culture and in two different sequential setups, for 4 h and 24 h. Transported metabolites 58 were investigated by UPLC-MS/MS E and the effects on NO production, ROS inhibition and 59 secretion of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8) and intercellular 60 adhesion molecule-1 (ICAM-1) were evaluated in TNF-α-activated and non-activated 61 endothelial cells. RSV and four conjugated metabolites, two sulfates and two glucuronides, 62 were identified after intestinal transport. In both co-culture and sequential systems, RSV at 63 20 µM strongly induced NO production. Changes in ROS and NO levels demonstrated a 64 clear effect of crosstalk between cells in the co-culture. The secretion of proinflammatory 65 cytokines and VEGF was largely increased by treatment with TNF-α (inflammatory 66 condition). The polyphenol intervention significantly reduced the levels of VEGF, ROS, IL-8 67 and ICAM-1, with a more pronounced effect in TNF-α-activated endothelial cells. In 68 conclusion, RSV and its metabolites showed accentuated bioactivity on TNF-α-induced 69 inflammation and the metabolism of endothelial cells as a biological target was not only 70 influenced by these phenolics, but also by the communication between distinct cell lines, 71 showing a new perspective for investigations on polyphenol intervention and its biological 72 outcomes.

Anti‐inflammatory potential of black carrot (Daucus carota L.) polyphenols in a co‐culture model of intestinal Caco‐2 and endothelial EA.hy926 cells

“…The production of NO in endothelial cells was monitored using the Griess colorimetric assay . For this purpose, equal volumes of the Griess reagent (Sigma‐Aldrich) and endothelial cell culture supernatant were mixed and incubated at room temperature for 15 min.…”

“…To date, only few studies investigated the anti‐inflammatory effects of polyphenols in co‐cultured intestinal epithelial and endothelial cells and yet application of this model is important due to the cross‐talk mechanisms between the two cell lines, which may have an indirect impact on endothelial function . Considering the above, the aim of the current study was to determine the potential of polyphenols from black carrot and its by‐products to modulate the inflammatory response in TNF‐α‐stimulated EA.hy926 endothelial cells co‐cultured with differentiated intestinal Caco‐2 cells.…”

Grape Peel Extract and Resveratrol Inhibit Wrinkle Formation in Mice Model Through Activation of Nrf2/HO‐1 Signaling Pathway

“…Grape and its products are well-documented to have numerous beneficial effects such as antioxidant, cardio-protective, anticancer, anti-inflammation, anti-aging, and antimicrobial properties (Toaldo et al, 2016;Xia, Deng, Guo, & Li, 2010).…”

A Comparative Study of Phenols in Apulian Italian Wines

“…Hydroxytyrosol is one of the most powerful antioxidants in nature, and extensive research has been carried out trying to exploit its therapeutic effects on the cardiovascular system, neurodegenerative diseases, cancer treatment, osteoporosis, and diabetic neuropathy, to name a few [15,16,17,18,19,20]. The stilbene trans -resveratrol has been one of the most extensively studied non-flavonoids due to its well-known health benefits, such as cardioprotective and chemopreventive effects (by inhibiting LDL oxidation) and anti-inflammatory, antibacterial, antifungal, antiviral, neuroprotective, antiproliferative, and anti-angiogenic activities [21,22,23,24,25]. …”