Chronic inflammatory diseases, including cardiovascular disorders, metabolic syndrome, autoimmune diseases, cancer, and neurodegenerative conditions, are driven largely by continuous activation of nuclear factor kappa-B (NF-κB) signalling. While NF-κB is recognized as a transcription factor regulating immune and inflammatory gene expression, emerging evidence demonstrates that NF-κB activity is tightly controlled through epigenetic mechanisms such as DNA methylation, histone modifications, chromatin remodelling, and non-coding RNA regulation. Dietary polyphenols have gained increasing attention as epigenetic modulators of this NF-κB signalling pathway. This review focuses on current advances in understanding how dietary polyphenols including resveratrol, curcumin, epigallocatechin gallate (EGCG), quercetin, genistein, fisetin, luteolin, and epicatechin regulate inflammatory signalling through epigenetic reprogramming. These compounds influence DNA methyltransferases, histone acetyltransferases, histone deacetylases, Silent Information Regulator T1(SIRT1) activation, and microRNA networks, ultimately reducing NF-κB p65 acetylation, suppressing transcriptional activation of pro-inflammatory genes, and restoring immune homeostasis. Evidence from experimental studies reveal the potential of these polyphenols in managing chronic inflammatory disorders like atherosclerosis, type 2 diabetes, rheumatoid arthritis, cancer, and neuroinflammatory disorders. Despite promising insights, translational challenges remain, including limited bioavailability, variability in metabolism, optimal dosing strategies, and potential epigenome-wide effects. Future studies integrating nutrigenomics, epigenomics, systems biology, and clinical trials are required to validate polyphenol-based interventions. Targeting the NF-κB–epigenetic axis is an innovative strategy for precision therapeutics and management of chronic inflammatory diseases through dietary and nutraceutical approaches.
NF-κB; Epigenetic regulation; Nutraceutical polyphenols; Chronic inflammation; DNA methylation; Histone modification.