Polyphenols and AGEs/RAGE axis. Trends and challenges

The formation of advanced glycation end-products (AGEs) is a key pathophysiological event linked not only to the onset and progression of diabetic complications, but also to neurodegeneration, cardiovascular diseases, cancer, and others important human diseases. AGEs contributions to pathophysiology are mainly through the formation of cross-links and by engaging the receptor for advanced glycation end-products (RAGE). Polyphenols are secondary metabolites found largely in fruits, vegetables, cereals, and beverages, and during many years, important efforts have been made to elucidate their beneficial effects on human health, mainly ascribed to their antioxidant activities. In the present review, we highlighted the beneficial actions of polyphenols aimed to diminish the harmful consequences of advanced glycation, mainly by the inhibition of ROS formation during glycation, the inhibition of Schiff base, Amadori products, and subsequent dicarbonyls group formation, the activation of the glyoxalase system, as well as by blocking either AGEs-RAGE interaction or cell signaling.