Advances in Understanding the Role of NRF2 in Liver Pathophysiology and Its Relationship with Hepatic-Specific Cyclooxygenase-2 Expression

Abstract

Oxidative stress and inflammation play an important role in the pathophysiological changes of liver diseases. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that positively regulates the basal and inducible expression of a large battery of cytoprotective genes, thus playing a key role in protecting against oxidative damage. Cyclooxygenase-2 (COX-2) is a key enzyme in prostaglandin biosynthesis. Its expression has always been associated with the induction of inflammation, but we have shown that, in addition to possessing other benefits, the constitutive expression of COX-2 in hepatocytes is beneficial in reducing inflammation and oxidative stress in multiple liver diseases. In this review, we summarized the role of NRF2 as a main agent in the resolution of oxidative stress, the crucial role of NRF2 signaling pathways during the development of chronic liver diseases, and, finally we related its action to that of COX-2, where it appears to operate as its partner in providing a hepatoprotective effect.

Cannabis sativa(Hemp) seed-derived peptides WVYY and PSLPA modulate the Nrf2 signaling pathway in human keratinocytes

“…Subsequently, it dimerizes with sMaf to facilitate the transcription of antioxidant responsive element-containing genes, such as SOD1, SOD2, HO-1, and CAT, to mediate the antioxidant mechanism [41,42]. Additionally, Nrf2 regulates the expression of enzymes involved in GSH production, quinone detoxification, and NADPH synthesis [43]. Moreover, the Nrf2 signaling pathway is involved in inflammation [34,44], cell viability [45], antibacterial activity [36,46], and wound healing [47,48].…”

Silymarin Synergizes with Antiviral Therapy in Hepatitis B Virus-Related Liver Cirrhosis: A Propensity Score Matching Multi-Institutional Study

“…The Nrf2 pathway functions as a cellular defense mechanism, crucial for protecting cells from oxidative stress and inflammation. Studies suggest that silymarin may activate the Nrf2 pathway, serving as a negative regulator of chronic inflammation in LC [ 59 ]. Additionally, considering the central role of HSCs in liver fibrosis [ 60 ], silymarin has been proposed to inhibit their activation [ 24 ].…”

Melissa officinalis extract palliates redox imbalance and inflammation associated with hyperthyroidism-induced liver damage by regulating Nrf-2/ Keap-1 gene expression in γ-irradiated rats

“…Abd Allah et al [ 75 ] demonstrated that M. officinalis extract activated Nrf2 in the hippocampus of epileptic rats. It is noteworthy that activation of the Nrf2 pathway enhanced the antioxidant defence system and minimize the production of ROS [ 46 , 76 ]. Furthermore, Wardyn et al [ 77 ] and Vasileva et al [ 78 ] revealed that the activated Nrf2 hampered the inflammatory cascade not only by suppressing NF-κB and pro-inflammatory mediators but also by activating the anti-inflammatory cytokines.…”