Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Figure 2

Nrf2 activity is augmented by exogenous and/or endogenous stressors. Under basal conditions, Keap1 mediates Nrf2 ubiquitination and subsequent proteasomal degradation through acting as an adaptor molecule for CUL-E3 ligase. Upon exposure to exogenous and/or endogenous stressors, such as xenobiotics and ROS, respectively, Nrf2 translocates into the nucleus and binds to the ARE to activate cytoprotective molecules, including antioxidant and detoxification enzymes. Superoxide dismutase (SOD) mediates the dismutation of superoxide radicals (O₂^-⋅) leading to the formation of hydrogen peroxide (H₂O₂). Catalase and glutathione peroxidase (GPx) catalyze the degradation of H₂O₂. HO-1 catalyzes degradation of heme to biliverdin and bilirubin which are potential antioxidants [49]. CO: carbon monoxide.