Phytochemicals as Epigenetic Modulators in Chronic Diseases; Molecular Mechanism

Phytochemicals are bioactive plant-derived compounds with significant antioxidant, anti-inflammatory, and epigenetic modulatory properties, offering promising avenues for the prevention and management of chronic diseases. Chronic conditions such as cancer, cardiovascular, neurodegenerative, metabolic, and autoimmune disorders often involve oxidative stress, inflammation, and epigenetic dysregulation. Evidence from in vitro and in vivo studies indicates that phytochemicals, including flavonoids, carotenoids, phenolic acids, organosulfur compounds, and terpenes, can attenuate oxidative damage by enhancing endogenous antioxidant defenses, modulate inflammatory signaling pathways such as NF-κB and Nrf2, and influence gene expression through the regulation of DNA methylation, histone modifications, and non-coding RNAs. Specific compounds—such as hesperidin, genistein, phloretin, lycopene, caffeic acid, p-coumaric acid, anacardic acid, allyl mercaptan, silybin, artemisinin, and geraniol—demonstrate multi-targeted actions, reversing aberrant epigenetic marks and restoring cellular homeostasis. By simultaneously acting on redox balance, inflammatory mediators, and epigenetic regulators, these natural compounds provide a mechanistic basis for chemoprevention and adjuvant therapy. However, translation into clinical applications requires rigorous trials to assess bioavailability, synergistic effects, and safety in humans. Understanding the molecular mechanisms of phytochemical action may advance novel, integrative strategies for chronic disease prevention and health promotion.