Protective effects of cyanidin-3-O-glucoside on human epithelial cells exposed to palmitic acid

The intestinal mucosal barrier represents a defensive barrier between the human body and the surrounding environment providing protection against luminal pathogens and antigenic molecules. An important factor of intestinal homeostasis and inflammation is the barrier integrity so that the dysfunction of intestinal mucosal barrier is key to the occurrence of severe intestinal disorders, including inflammatory bowel diseases (IBDs). Recently, epidemiological studies reported obesity and metabolic syndrome as risk factors in IBDs development. In fact, increased serum free fatty acids (FFA), or adipokines and cytokines, taken up into the enterocyte via the basolateral membrane, are supposed to be potential modulators of intestinal inflammation. In addition, increased FFA uptake is associated to notice able morphological alterations and cytokines and chemokines release from the intestinal cells so activating and recruiting immune cells. However, even if the mechanisms involved in the observed effects remain unclear, it has been suggested the involvement of arachidonic acid cascade with resultant increased derivatives (PGE2, TBXs, etc), altered cell membrane fluidity, intracellular oxidative stress, and the activation of NF-kB proinflammatory pathway. Many studies reported the effects of anthocyanins, a class of flavonoid compounds widely distributed in the Mediterranean diet, in various chronic inflammatory diseases, such as IBDs. In particular, anthocyanins are able to inhibit the release of proinflammatory cytokines, acting via reduced NF-κB expression and translocation, apoptosis, and oxidative stress probably via activation of cellular adaptive responses triggered by the Nrf2 transcription factor. The aim of this work was to evaluate some of the intracellular mechanisms involved in fatty acid modulation of intestinal epithelial inflammation by using an in vitro intestinal epithelial system consisting of filter grown Caco-2 monolayers, and the effects exerted by cyanidin-3-O-glucoside (C3G) pretreatment. Caco-2 cells basolateral exposure to palmitic acid (PA) for 6 h induced intracellular oxidative stress. Interestingly, C3G pretreatment was able to reduce reactive oxygen species and intracellular total antioxidant power. Furthermore, PA activated NF-kB proinflammatory pathway and induced IL8 gene and COX-2 protein expression. On the contrary, cells pretreatment for 24h with C3G was effective in preventing PA-induced changes. In conclusion, C3G improved intracellular redox status altered by PA in Caco-2 cells and showed anti-inflammatory properties through the modulation of NF-kB pathway. These data suggest that anthocyanins could contribute, as complementary approaches to the conventional already existing therapeutic approaches (i.e. non-steroidal anti-inflammatory drugs) to the management of IBDs