Mechanistic role of Nrf2 modulators in lipid peroxidation: a perspective towards carcinogenesis

The brain lipid profile is a complex and dynamic system playing a critical role in regulating various functions, including mood swings, perception, and emotional behavior. Explicitly, the enrichment of polyunsaturated fatty acids (PUFAs) in the brain and membranes exposes them to reactive free radical species [reactive oxygen species (ROS)/reactive nitrogen species (RNS)], leading to lipid peroxidation (LP), which may result in disruption of cell fluidity and membrane permeability, hindering cellular functions. An increase in LP end products specifically triggers apoptosis and necrosis, potentially resulting in the onset of serious ailments such as neurodegenerative diseases, cancer, atherosclerosis, and diabetes. Cells are equipped with antioxidant defense systems to combat and scavenge harmful reactive free radical species, thereby maintaining redox homeostasis. Indisputably, the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a key player in regulating the cellular antioxidant response by controlling gene expression related to oxidative and electrophilic stress. Nrf2 also influences various cellular processes such as metabolism, inflammation, drug detoxification, and DNA repair. In recent years, several compounds have emerged as Nrf2 modulators, including curcumin, quercetin, anthocyanins, tea polyphenols, kaempferol, hesperetin, and icariin. These compounds play a vital role in regulating various essential Nrf2 upstream activators, thereby modulating Nrf2 pathways, predominantly upregulated by several phytochemical compounds, such as terpenoids like monoterpenes (aucubin, catapol), diterpenes (ginkgolides), triterpenes (ginsenosides), and carotenoids (astaxanthin, lycopene). This review is a modest attempt to provide a comprehensive literature appraisal, facilitating a deeper understanding of the significant role of Nrf2 modulators in obstructing LP and treating serious diseases such as cancer.