Department of Basic Medical Sciences Neuroscience and Sensory Organs University of Bari, Bari, Italy
It is well known that dietary polyphenols and those contained in functional foods and nutraceuticals exert both anti oxidant and anti inflammatory activities. Over recent years, we have disclosed three different mechanisms of action, accounting for the polyphenol-mediated anti inflammatory function. 1. Using polyphenols extracted from red wine (Negroamaro cultivar), we have demonstrated their ability to in vitro inhibit the binding of bacterial endotoxins to the human peripheral blood monocyte toll-like receptor-4. This event has been shown to lead to a reduced activation of the NFk-B pathway and diminished secretion of proinflammatory cytokines. 2. Fermented grape marc (FGM) from both Negroamaro and Koshu Vitis vinifera coud in vitro induce the transcription factor Foxp3 in CD4+ human peripheral blood lymphocytes from normal donors. Then, Foxp3+ CD4+ cells converted into T regulatory cells able to release interleukin (IL)-10, an anti inflammatory cytokine, in polyphenol-stimulated lymphomonocyte culures. This mechanism seems to account for the attenuation of murine experimental colitis following oral administration of Koshu FGM. This treatment prevented shortening of the bowel and markedly reduced release of IL-1 beta and tumor necrosis factor-alpha in colitis mice. 3. Polyphenols extracted from seeds of red grape (Nero di Troia cultivar) were in vitro tested for their anti inflammatory activity on human obese peripheral blood lymphomonocytes. Evaluation of cytokines released in the supernatants of polyphenol-stimulated lymphomonocytes demonstrated a reduced release of IL-6, an acute phase reactant, likely involved in the development of cardiovascular events in obese people. At the same time, the evidence for a reduced production of IL-21, which, in turn, inhibit s T helper- 17 activation suggests a novel anti inflammatory mechanism. In fact, it is well know that T h-17 cells release IL-17, which is an inflammatory cytokine and whose levels were significantly reduced in our test system.
Conclusively, the demonstration of different pathways activated by polyphenols to induce anti inflammatory activity suggests their potential use, as nutraceuticals, in various clinical settings.
These experiments were in part supported by a grant from D.A.R.E (Pro.Ali.Fun.), Rome (Italy).