Abstract
Oxidative stress is the leading player in the onset and development of various diseases. The Keap1-Nrf2 pathway is a pivotal antioxidant system that preserves the cells’ redox balance. It decreases inflammation in which the nuclear trans-localization of Nrf2 as a transcription factor promotes various antioxidant responses in cells. Through some other directions and regulatory proteins, this pathway plays a fundamental role in preventing several diseases and reducing their complications. Regulation of the Nrf2 pathway occurs on transcriptional and post-transcriptional levels, and these regulations play a significant role in its activity. There is a subtle correlation between the Nrf2 pathway and the pivotal signaling pathways, including PI3 kinase/AKT/mTOR, NF-κB and HIF-1 factors. This demonstrates its role in the development of various diseases. Curcumin is a yellow polyphenolic compound from Curcuma longa with multiple bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Since hyperglycemia and increased reactive oxygen species (ROS) are the leading causes of common diabetic complications, reducing the generation of ROS can be a fundamental approach to dealing with these complications. Curcumin can be considered a potential treatment option by creating an efficient therapeutic to counteract ROS and reduce its detrimental effects. This review discusses Nrf2 pathway regulation at different levels and its correlation with other important pathways and proteins in the cell involved in the progression of diabetic complications and targeting these pathways by curcumin.
Highlights
Under hyperglycemic condition, increasing the glucose flux promotes the production of superoxide anion O2 .- in the mitochondrial electron-transport chain, which in turn induces the production of AGE products, activation of Protein Kinase C (PKC) and hexosamine pathways, and as a result the formation of secondary reactive oxygen species [118], including peroxynitrite and hydroxyl radicals [119]
It is appropriate to conclude that the Keap1-Nrf2 pathway has a fundamental role in the onset and progress of various inflammatory diseases
The pivotal role of this pathway and its correlation with various signaling pathways and factors indicates an extensive internal network in the development of different diseases; according to the description provided in this review, some diseases and their complications are directly related to oxidative stress in cells
Summary
Cells develop non-enzymatic and enzymatic antioxidant systems to protect themselves from inflammation and pathogenesis of a broad range of oxidative stress-related diseases [10,11]. Some studies have shown decreased antioxidant response in cells leads to various diseases, including diabetes, cancer, and AD. Among these diseases, diabetes and its complications have a high prevalence today. Exogenous and endogenous ROS and electrophiles induce the cytosolic two Keap and one Nrf complex toward nuclear translocation of Nrf where it binds to antioxidant response elements after making complex with sMAF protein (Nrf2-sMaf) to trigger transcription of cytoprotective genes of phase. The therapeutic applications of curcumin in reducing diabetes and its complications are discussed
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