NF-E2-related factor 2 (NFE2L2 or Nrf2), a basic leucine zipper transcription factor that belongs to the Cap “N” Collar (CNC) family of transcription factors is expressed in diverse cell types including hepatocytes (Oyake et al., 1996). Activated by electrophiles and oxidants, Nrf2 binds to DNA sequences which named antioxidant response elements (ARE), and initiates the transcription of target genes that contribute to elimination of free radicals and electrophiles (Wakabayashi et al., 2004). In other words, Nrf2 is a key nuclear transcription factor that regulates the expression of genes against oxidative stress. Nrf2 is reported to play a cytoprotective role in NAFLD by regulating the expression of antioxidants and cytokines, thus resisting oxidation, inflammation, and fibrosis which generate the second hit of the “two-hit” theory (Chowdhry et al., 2010; Sugimoto et al., 2010; Meakin et al., 2014). Deficiency of Nrf2 in mice leads to rapid onset and progression of NAFLD. Thus, the potential of Nrf2 as the treatment target of NAFLD has been demonstrated using Nrf2 activators in vivo and in vitro (Shimozono et al., 2013).
