From translational medicine to functional foods: Mechanistic insights and therapeutic applications of hormetic phytochemicals

• Dietary phytochemicals benefit health by inducing hormetic stress responses. • Hormetic phytochemicals show biphasic effects: low dose protects, high dose harms. • Moderate intake of hormetins activates adaptive cellular defense mechanisms. • Plant hormetins act as antioxidant, anti-inflammatory, and cytoprotective agents. • In functional and fortified foods, hormetins show strong translational potential. Dietary phytochemicals, also termed nutritional hormetins, are gaining attention for their ability to induce hormesis. Hormesis describes a biphasic dose-response, where low-to-moderate exposure activates adaptive cellular defenses, while higher doses may be detrimental. Plant-derived compounds such as curcumin, luteolin, allicin, sulforaphane, and tomatidine trigger stress-response pathways mediated by diverse transcription factors and kinases. Notable examples include AMPK-mediated activation of Sirtuin-1, and Nrf2 and FOXO signaling, which regulate antioxidant enzymes, neurotrophic factors, and cytoprotective proteins. Regulation of these pathways offers a promising strategy against both communicable and non-communicable diseases. In infections, hormetic phytochemicals enhance host immunity and restrict pathogen survival. In non-communicable diseases such as diabetes, obesity, cancer, and neurodegeneration, they strengthen antioxidant defense, modulate glucose metabolism, suppress chronic inflammation, induce apoptosis of abnormal cells, and restore neuronal resilience. Substantial evidence supports their target-specific actions, pathway regulation, systemic protection, and safety for human use. Incorporation of such phytochemicals into fortified and functional foods presents a sustainable, cost-effective approach for prevention and management of global health challenges. Thus, hormetic phytochemicals provide an innovative strategy bridging traditional medicine and modern therapeutics. This review highlights their role in hormetic cellular responses, therapeutic applications, and potential in functional food development.