Inhibition of the pro‐inflammatory NF‐κB pathway by a grape seed and grape marc meal extract in intestinal epithelial cells

Abstract

In pigs and other monogastric animal, the weaning phase is commonly accompanied by an increased susceptibility to gut disorders such as diarrhoea owing to the induction of an inflammatory process in the intestine during weaning. Given the unfavourable effects of intestinal inflammation on feed consumption, digestive capacity of the intestine and growth of animals, controlling intestinal inflammation is a reasonable approach for the maintenance of performance characteristics of livestock animals. Therefore, this study aimed to study the anti-inflammatory potential of a commercial polyphenol-rich grape seed (GS) and grape marc (GM) meal-based feed additive in a well-established in vitro intestinal epithelium model (polarized Caco-2 cells). The anti-inflammatory potential was evaluated by studying the effect of an ethanolic extract obtained from the GS and GM meal-based feed additive (GSGME) on the pro-inflammatory transcription factor NF-κB, which is considered to play a key role in the induction of weaning-associated intestinal inflammation. The highest non-cytotoxic concentrations of the ethanolic GSGME dose dependently reduced TNFα-induced NF-κB transactivation and decreased TNFα-induced mRNA levels of the NF-κB target genes IL-1β, IL-8, MCP-1 and CXCL1 in Caco-2 intestinal cells (p < 0.05). No effect of the ethanolic GSGME was observed on the cytoprotective Nrf2 pathway in Caco-2 cells as evidenced by an unaltered Nrf2 transactivation and unchanged mRNA levels of Nrf2 target genes, such as GPX-2, NQO1, CYP1A1 and UGT1A1. In conclusion, this study shows that an ethanolic GSGME exerts anti-inflammatory effects in intestinal cells under in vitro conditions. Thus, polyphenol-rich GSGM meal-based feed additives may be useful for the inhibition or prevention of inflammatory processes in the intestine of livestock animals, in particular during states with inappropriate NF-κB activation in the intestinal tissue, such as the weaning phase. Future studies are warranted to prove the in vivo anti-inflammatory potential of GSGM meal-based feed additives.

Wine consumption and intestinal redox homeostasis

“…Interestingly, this wine extract induced miR-126, a microRNA that is involved in negative regulation of vascular cell adhesion molecule-1 expression [66]. CaCo-2 cells treated with TNF-α confirmed the anti-inflammatory effect of grape seeds and of grape marc meal-based feed additives used for livestock nutrition, in that they inhibited NF-κB transactivation and IL-1β, IL-8, monocyte chemotactic protein-1, chemokine CXC ligand 1 expression [67].…”

Effects of diets containing grape seed, linseed, or both on milk production traits, liver and kidney activities, and immunity of lactating dairy ewes

“…Previous in vitro studies showed a similar inhibitory effect of polyphenols in human cells (Williamson et al, 2006) and in murine splenocytes (Yamanaka et al, 2012). In addition, Gessner et al (2012) found antiinflammatory effects of phenolic compounds extracted from grape seeds and grape marc in intestinal cells under in vitro conditions. Conversely, lymphocyte-derived cytokines increased in serum samples of calves fed polyphenols extracted from pomegranate, thus showing an immune-stimulatory effect (Oliveira et al 2010).…”

Mecanismos moleculares de ação anti-inflamatória e antioxidante de polifenóis de uvas e vinho tinto na aterosclerose

“…Os polifenóis do vinho parecem modular a atividade do AP-1 por meio da inibição da PKC, da via MAPK e/ ou alterando a ligação do AP-1 ao DNA. Gessner et al (2012) constatatam que o efeito anti-inflamatório de extratos obtidos de farinhas de semente e de bagaço de uva também ocorre via inibição da via NF-kB. Em macrófagos humanos com inflamação mediada pelo LPS, extratos de uva (Vitis labrusca) em pó (GPE) atenuaram a fosforilação da JNK e p38 e diminuíram a degradação do IkBá e a fosforilação da c-Jun, bem como bloquearam o NF-kB.…”