Phytochemicals as Epigenetic Modulators in Chronic Diseases: Molecular Mechanisms

Phytochemicals are plant-derived bioactive compounds with antioxidant, anti-inflammatory, and epigenetic modulatory effects that may contribute to the prevention and management of chronic diseases. This review synthesizes recent evidence on the molecular mechanisms through which phytochemicals influence oxidative stress, inflammatory signaling, and epigenetic regulation. A targeted literature search of the PubMed and Web of Science databases (2015–2025) identified over 400 experimental and review studies investigating phytochemicals with documented antioxidant and epigenetic activities. Eligible articles were selected based on relevance to oxidative stress, inflammation, and DNA or histone modification pathways in chronic diseases. Data were qualitatively analyzed to highlight mechanistic links between redox balance, transcriptional regulation, and disease modulation. The results indicate that several phytochemicals, including hesperidin, phloretin, lycopene, and silybin, modulate signaling cascades—NF-κB, Nrf2, and PI3K/Akt—while also influencing DNA methylation and histone acetylation to restore gene expression homeostasis. Despite strong in vitro and in vivo evidence, translation to clinical practice remains limited by low bioavailability, lack of standardized formulations, and insufficient human trials. Future research should prioritize integrative study designs linking molecular mechanisms to clinical endpoints. Understanding the epigenetic actions of phytochemicals may guide the development of nutraceutical strategies for chronic disease prevention.