• Hormetic phytochemicals activate Nrf2, AMPK, and sirtuins to boost cellular defense systems. • Nutraceuticals offer non-toxic, adaptive support against chronic inflammation and oxidative stress. • Polyphenols and flavonoids enhance mitochondrial function and metabolic resilience in humans. • Hormetic agents show promise in treating aging, neurodegeneration, and cardiometabolic disorders. • Bioactives enable functional foods, personalized nutrition, and immune-enhancing health strategies. Phytochemicals and nutraceuticals are the focus of substantial interest because of their potential to modulate human health by adaptive change in biological response. Evidence is growing that many of the bioactive compounds exert their modulation on beneficial effects based on hormesis, a biphasic dose–response phenomenon in which low doses stimulate protective cell-based mechanisms while high concentrations can have toxic action. Natural bioactive dietary compounds including polyphenols, flavonoids, terpenoids, alkaloids and organosulfur species from plant-based foods have been found to modulate fundamental signaling networks that govern redox balance, inflammation, energetic status and resilience of cells such as the Nrf2, AMPK, sirtuins and mitochondrial stress response pathways. More recent evidence also indicates that the health effects of these compounds are not due solely to their direct antioxidant activity but derive from their capacity to induce mild stress responses in cells, stimulating endogenous defense mechanisms. This review comprehensively compiles molecular, cellular and systemic data connecting bioactive-rich dietary sources to hormesisal regulation and adaptive stress responses. The objective of this review is to present a mechanistic and integrative perspective on the manner in which hormetic modulation of human health is influenced by bioactive phytochemicals and nutraceuticals.
Surisetti et al. (Wed,) studied this question.