From antioxidant to signal modulator: The expanding role of quercetin in human health

Quercetin, a naturally occurring flavonoid widely distributed in fruits, vegetables, and medicinal plants, has attracted considerable attention as a safe and affordable therapeutic candidate for the prevention and management of lifestyle and age-related diseases. Extensive evidence demonstrates that quercetin exerts potent antioxidant, anti-inflammatory, antiviral, chemoprotective, and immunomodulatory effects through modulation of multiple signalling pathways, including Nrf2, AMPK, SIRT1, NFκB, Wnt/β-catenin, and p53. Activation of Nrf2, AMPK, and SIRT1 enhances endogenous antioxidant defenses and maintains cellular redox homeostasis, whereas inhibition of NF-κB and MAPK suppresses the production of pro-inflammatory mediators. In addition, quercetin regulates apoptosis and cell cycle progression through p53, PI3K/Akt, and mitochondrial signalling pathways, highlighting its relevance in cancer prevention and therapy. This review comprehensively examines the molecular mechanisms, preclinical evidence, and emerging clinical applications of quercetin in oxidative stress-related disorders, chronic inflammatory diseases, metabolic dysfunction, neurodegenerative conditions, and cancer. Clinical studies further suggest that quercetin may provide therapeutic benefits in chronic obstructive pulmonary disease, sarcoidosis, hyperuricemia, cardiovascular disease, and SARS-CoV-2 infection, although results remain heterogeneous. Despite its broad pharmacological potential, poor aqueous solubility, extensive metabolism, and low oral bioavailability continue to limit its clinical translation. Overall, quercetin represents a promising multitarget phytoconstituent, and future advances in formulation technologies and well-designed clinical trials are expected to clarify and expand its therapeutic utility.