ANTHOCYANINS AND CELLULAR REDOX SIGNALING: NRF2 AND NF-KB AS TARGETS

Abstract

Reactive oxygen species (ROS) serve important physiological functions in host defense, and constitute an important second messenger in cell signaling transduction, but several chronic pathological conditions are associated with a status of oxidative stress, that is an unbalance between ROS formation and antioxidant availability. Many plant antioxidants, have been shown able to prevent free radical-related diseases by counteracting cell oxidative stress. However it is now considered that the in vivo beneficial effects of these phytochemicals are unlikely to be explained just by their antioxidant capability. Several plant antioxidants like anthocyanins exhibit hormetic properties, by acting as ‘low-dose stressors’ that may prepare cells to resist more severe stress. The discovery of specific genes (HO-1, NQO1, g-GCS) and pathways (redox sensitive Nrf2, NF-kB regulated signaling) affected by antioxidants, led to the hypothesis that anthocyanins may act as modulators of gene regulatory and signal transduction pathways. Since activation of endogenous cellular defense mechanisms can represent an innovative approach to therapeutic intervention in pathological conditions characterized by chronic tissue damage, a better understanding of adaptive response mechanisms induced by plant antioxidants at the cellular and molecular levels can lead to novel strategies for the prevention and treatment of many different diseases. The adaptive responses induced by anthocyanins, as well as the molecular mechanisms involved in such responses, will be discussed.