Sesamin Activates Nrf2/Cnc-Dependent Transcription in the Absence of Oxidative Stress in Drosophila Adult Brains

Abstract

Sesamin, a major lignin in sesame seeds, possesses health-promoting properties. Sesamin feeding suppresses several aging-related phenotypes such as age-dependent accumulation of damaged proteins in the muscles and neuronal loss in the brains of Drosophila adults with high levels of reactive oxygen species. Sesamin promotes the transcription of several genes that are responsible for oxidative stress, although the underlying mechanism remains unclear. Here, we aimed to demonstrate that sesamin mediates its action through activation of a transcription factor, Nrf2 (Cnc in Drosophila), essential for anti-aging oxidative stress response. Nrf2/Cnc activation was determined using the antioxidant response element, Green Fluorescence Protein reporter, that can monitor Nrf2/Cnc-dependent transcription. We observed strong fluorescence in the entire bodies, particularly in the abdomens and brains, of adult flies fed sesamin. Interestingly, Nrf2/Cnc was strongly activated in neuronal cells, especially in several neuron types, including glutamatergic and cholinergic, and some dopaminergic and/or serotonergic neurons but not in GABAergic neurons or the mushroom bodies of flies fed sesamin. These results indicate that the anti-aging effects of sesamin are exerted via activation of Nrf2/Cnc-dependent transcription to circumvent oxidative stress accumulation in several types of neurons of adult brains. Sesamin could be explored as a potential dietary supplement for preventing neurodegeneration associated with accumulation of oxidative stress.

Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities

“…Sesamin protected against ulcerative colitis in colorectal adenocarcinoma Caco-2 cells injured by H 2 O 2 -induced oxidative stress [ 113 ]. Sesamin feeding protected adult Drosophila against oxidative damage [ 171 ].…”

Sesamin Metabolites Suppress the Induction of Cellular Senescence

“…Since upregulation of the antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione S-transferase by SC1 are reported [ 46 , 47 ], there is also a possibility that the increase of intracellular antioxidative activities is related to the suppression of cellular senescence. It was demonstrated that sesamin protected Drosophila adults against oxidative damage via stimulation of the Nrf2/Cnc-dependent transcription in the adult gut and brain [ 48 ]. Elucidation of the mechanisms of action with SC1 and EC1-2 is the next issue for future study.…”

Protective Effects of Sesamin on Cytoxan-Induced Spermatogenesis Dysfunction by Regulating RNF8-ubH2A/ubH2B Pathways in Male Mice

“…Sesamin commonly induces hormetic dose responses in numerous biological models for endpoints of biomedical and clinical relevance. For example, sesamin can prevent neurodegeneration related to the accumulation of oxidative stress by regulating the Nrf2-ARE pathway ( Calabrese et al, 1996 ; Le and Inoue, 2021 ). Sesamin can inhibit the proliferation and invasion of cancer cells and can be used as a drug to prevent and treat cancer ( Mottaghi and Abbaszadeh, 2021 ).…”

“…Sesamin commonly induces hormetic dose responses in numerous biological models as endpoints of biomedical and clinical relevance. For example, sesamin can prevent neurodegeneration related to the accumulation of oxidative stress by regulating the Nrf2-ARE pathway ( Fusco et al, 2021 ; Le and Inoue, 2021 ). The Nrf2-ARE axis plays a key role as an important signal to protect cells from endogenous and exogenous oxidative stress ( de Freitas Silva et al, 2018 ).…”