Influence of Polyphenol-Dense Residues: Wine Pomace, Coffee and Brewing By-Products, on Nrf2-Mediated Cellular Defense Mechanisms: A Review
Dina Tenji1, Nina Tomić2, Marija Petrović3, Marina Jovanović3,*
1 Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, Novi Sad, Serbia
2 Institute of Technical Sciences of SASA, University of Belgrade, Knez Mihailova 35/IV, Belgrade, Serbia
3 Institute of General and Physical Chemistry, Studentski trg 12/V, Belgrade, Serbia
* Corresponding Author: Marina Jovanović. Email: 
(This article belongs to the Special Issue: Advances in Nrf2 Signaling Pathway in Neurodegenerative Diseases)
BIOCELL https://doi.org/10.32604/biocell.2026.083171
Received 30 March 2026; Accepted 25 June 2026; Published online 09 July 2026
Abstract
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a central regulator of cellular defense mechanisms. It coordinates antioxidant responses, redox homeostasis, inflammation control, mitochondrial function, intracellular iron dynamics, glucose metabolism, lipid metabolism, and proteostasis. Dietary polyphenols can effectively modulate Nrf2 by directly activating the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2-antioxidant response elements (ARE) pathway and by indirectly influencing upstream kinases, epigenetic processes, and metabolites produced by the gut microbiota. By-products, generated in large quantities by the beverage industries, represent an abundant yet underexploited source of polyphenol-rich bioactive compounds. This narrative review critically summarizes current knowledge on molecular mechanisms of Nrf2 signaling, examines the role of dietary polyphenols as Nrf2-linked senotherapeutic agents, and reviews evidence supporting the Nrf2-modulating potential of major categories of polyphenol-rich by-products, coffee by-products (pulp, husk, silver skin, spent coffee ground), wine pomace, and brewing by-products (brewer’s spent grain, brewer’s spent yeast). Finally, key limitations, safety considerations, and research gaps for future investigations have been addressed. Polyphenol-rich agri-food by-products represent a promising tool for modulating endogenous stress-response pathways associated with longevity and may serve as sustainable Nrf2-targeted nutritional interventions, although challenges such as limited bioavailability remain.
Keywords
Nuclear factor erythroid 2-related factor 2 signaling; polyphenols; wine pomace; coffee by-products; brewer’s spent grain; brewer’s spent yeast; cellular defense; senotherapeutics; functional foods
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