FIGURE 2.

Activation of NRF2 pathway under oxidative stress. The regulation of NRF2 involves three distinct E3 ubiquitin ligase complexes: the KEAP1–CUL3–RBX1 complex, the β‐TrCP–SKP1–CUL1–RBX1 complex, and HRD1. When exposed to oxidative stress, ubiquitination processes transpire within these complexes, leading to the liberation of Nrf2. Upon its migration to the nucleus, Nrf2 binds to the antioxidant response element (ARE), triggering the expression of antioxidant proteins. This activation suppresses the release of proinflammatory cytokines and facilitates the detoxification of ROS. Nrf2, nuclear factor erythroid 2‐related factor 2; Keap, kelch‐like ECH‐associated protein 1; Cul3, Cullin‐3; RBX1, Ring box 1; β‐TrCP, β‐ transducin repeats‐containing proteins; SKP1, the S‐phase Kinase‐Associated Protein 1; HRD1, HMG‐coA reductase degradation protein 1; HO‐1, heme oxygenase‐1 signaling; GSH, glutathione; SOD, superoxide dismutase 1; CAT, catalase.