Down regulation of NF-kappa B as a therapeutic strategy for type 1 diabetes: effect of flavonoids

Nuclear factor-kappa B (NF-κB) is a redox-sensitive transcription factor that plays a critical role in the regulation of a variety of genes important in cellular responses, including inflammation, innate immunity, growth, and cell death. There are growing evidences that activation of NF-κB by acute oxidative stress may be the critical signal initiating the cascade of events leading to β-cell death and type 1 diabetes. This activation results in an increase in inflammatory and immune responses and leads to an amplification of reactive oxygen species (ROS) and nitric oxide (NO) production which, in turn, ultimately leads to the destruction of the β-cells, hyperglycemia and the development of type 1 diabetes. The key role of NF-κB in controlling the expression of multiple inflammatory and immune genes involved in type 1 diabetes makes this factor as a central and favorable target for therapeutic intervention of this disease. Polyphenolic plant-derived flavonoids display characteristic inhibitory patterns toward the NF-κB signal transduction pathways. In various types of cells, flavonoids, as natural polyphenolic antioxidants, strongly block cytokine- or LPS-induced NF-κB activation, which is crucial for iNOS expression in β-cells. Recently, we have suggested that a number of flavonoids might exert protective effects on pancreatic β-cell and therefore this could be considered as potential therapeutic agents for type 1 diabetes. On the other hand, studies investigating cytokine-induced pancreatic β-cells death models of type 1 diabetes, have found that flavonoids are effective for type 1 diabetes at least partly through inhibition of NF-κB activation. The importance of NF-κB in β-cell inflammatory responses is underscored by the fact that blockade of NF-κB in in vitro and in vivo models, by means of flavonoids, may prevents β-cell destruction and type 1 diabetes. In view of their anti-inflammatory and antioxidant abilities and their capacity to modulate NF-κB signaling pathways, it is hypothesize that flavonoids hold great promise as potential therapeutic agents for controlling the onset of type 1 diabetes.