Anti-inflammatory activity of Vitis vinifera L. leaves extract at gastrointestinal level

Gastrointestinal inflammations are pathologies largely diffused in the occidental countries. It has been demonstrated that gastric epithelial cells, after H. pylori infection, show higher levels of cytokines including IL-1\u3b2, TNF-\u3b1, and IL-8. This response strictly depends on the activation of NF- \u3baB, a transcription factor crucial in inflammation (1). Inflammatory bowel diseases (IBDs), as Crohn\u2019s disease, are pathologies of the gut involving NF-\u3baB (2), characterized by a dysregulation of the immune response against the enteric microflora. To treat gastro-intestinal inflammations is important to find new therapies and dietary approaches. Red dried leaves of grapevine (Vitis vinifera L., var. teinturiers, Vitaceae) are largely diffused in a variety of food supplements; however, the anti-inflammatory activity of the drug in the gastrointestinal tract has not been previously reported. The aim of the present work is to investigate the biological activity of an aqueous extract from Vitis vinifera L. dried leaves (VE) in an in vitro model of gastro-intestinal inflammation. We studied the inhibition of NF-\u3baB translocation and driven transcription (NFtrscr), and the effect on IL-8 release in gastric (AGS) and intestinal (Caco-2) epithelial cell lines, stimulated with TNF\u3b1 or IL-1\u3b2. The effects of one hour pre-treatment and the contribution of gastric (VEg) and intestinal (VEi) in vitro digestions of VE were also investigated. At gastric level VE and VEg inhibited in a concentration-dependent manner NFtrscr induced by TNF-\u3b1 (IC50 of 17.3 \u3bcg/mL and 15.5 \u3bcg/mL, respectively). Pre-treatment of AGS with VE had a lower inhibition of NFtrscr induced by TNF-\u3b1 compared to treatment, but no differences comparing IL-1\u3b2 stimulated conditions. VE in general was less active when IL-1\u3b2 was used as stimulus, except for NF-\u3baB translocation, where the effect was already significant at 10 \u3bcg/mL. VE and VEg were also able to inhibit IL-8 release induced by TNF-\u3b1 with approximately 70% and 50% inhibition at 100 \u3bcg/mL. At the intestinal level VE obtained an IC50 of 1.34 \u3bcg/mL in NFtrscr induced by TNF-\u3b1, but VEi was active only starting from 100 \u3bcg/mL, losing part of its activity after digestion. Pre-treatment of VE had a better inhibition of NFtrscr compared to treatment in Caco-2 stimulated by IL-1\u3b2, but no changes when TNF-\u3b1 was used. VE and VEi were able to reduce IL-8 secretion induced by IL-1\u3b2 in Caco-2, both obtaining approximately 50% inhibition at 100 \u3bcg/mL; in vitro digestion of the extract did not altered its biological activity in this parameter. The present study provides some experimental evidences of the anti-inflammatory activity of VE in the gastrointestinal tract. If these results will be confirmed by other studies, consumption of food supplements containing Vitis vinifera L. extracts might be useful to treat or prevent gastrointestinal inflammation