Nuclear factor erythroid 2-related factor 2-mediated signaling and metabolic associated fatty liver disease

Abstract

Oxidative stress is a key driver in the development and progression of several diseases, including metabolic associated fatty liver disease (MAFLD). This condition includes a wide spectrum of pathological injuries, extending from simple steatosis to inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Excessive buildup of lipids in the liver is strictly related to oxidative stress in MAFLD, progressing to liver fibrosis and cirrhosis. The nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of redox homeostasis. NRF2 plays an important role for cellular protection by inducing the expression of genes related to antioxidant, anti-inflammatory, and cytoprotective response. Consistent evidence demonstrates that NRF2 is involved in every step of MAFLD deve-lopment, from simple steatosis to inflammation, advanced fibrosis, and ini-tiation/progression of hepatocellular carcinoma. NRF2 activators regulate lipid metabolism and oxidative stress alleviating the fatty liver disease by inducing the expression of cytoprotective genes. Thus, modulating NRF2 activation is crucial not only in understanding specific mechanisms underlying MAFLD progression but also to characterize effective therapeutic strategies. This review outlined the current knowledge on the effects of NRF2 pathway, modulators, and mechanisms involved in the therapeutic implications of liver steatosis, inflammation, and fibrosis in MAFLD.

Capsaicin acts as a novel NRF2 agonist to suppress ethanol induced gastric mucosa oxidative damage by directly disrupting the KEAP1-NRF2 interaction

“…CAP, a natural small molecule derived from chili peppers, has been identified and verified to modulate the KEAP1-NRF2-ARE pathway in our study. This signaling plays a key role in several cancerous and non-cancerous diseases [33][34][35][36][37] . Therefore, it is a promising therapeutic target for combatting free radical damage associated with numerous conditions, including Alzheimer's disease 38 , chronic kidney disease 39 , cardiovascular disease 40 , cancer and aging 41 .…”

Plantamajoside modulates immune dysregulation and hepatic lipid metabolism in rats with nonalcoholic fatty liver disease viaAMPK/Nrf2 elevation

“…36 Nrf2 plays an important role in neutralizing oxidative stress and conserving redox homeostasis in the cell through the generation of cytoprotective and antioxidant enzymes, such as HO-1 and NQO1. 37 The role of Nrf2 in liver steatosis, inflammation, fibrosis, as well as related therapeutic strategies has been recently summarized by Bukke et al 38 Besides, the studies that the natural plants components alleviate NAFLD via AMPK/Nrf2 pathway have been reported extensively. 36,39,40 In this study, the downregulation in the relative protein level of p-AMPK/AMPK, Nrf2, and HO-1 in HFD-feeding rats was restored by the treatment of PMS, suggesting that PMS activated the AMPK/Nrf2 pathway in HFD-induced NAFLD rats.…”

Formation of EGCG oxidation self-assembled nanoparticles and their antioxidant activity in vitro and hepatic REDOX regulation activity in vivo

“…Nuclear factor erythroid 2-related factor 2 (NRF2) plays a central role in the regulation of cellular defense mechanisms against environmental stresses, especially in maintaining liver REDOX homeostasis under oxidative stress. 19 Additionally, the transcription activation of two-phase detoxification and antioxidant enzymes, including thioredoxin reductase (TrxR), thioredoxin (Trx), glutathione reductase (GR), glutaredoxin (Grx), glutathione S-transferase (GST), and glutathione peroxidase (GPx), can clear cellular oxidative stress and maintain REDOX balance. 20 Previous studies demonstrated that moderate reactive oxygen species (ROS) generated using EGCG (55 mg kg −1 ) by intraperitoneal injection (i.p.)…”