Abstract

Oxidative stress plays a central role in the pathogenesis of a wide range of human diseases, including 
cardiovascular diseases, neurodegeneration, cancer, diabetes, and inflammatory disorders. Natural 
antioxidants-compounds derived from dietary sources, medicinal plants, and isolated bioactive constituents such as 
vitamins, flavonoids, carotenoids, and polyphenols-offer biological modulation of reactive oxygen and nitrogen 
species (RONS) and influence numerous molecular targets linked to disease progression. These compounds 
scavenge free radicals, regulate redox-sensitive signaling pathways, and modulate gene expression through direct 
and indirect mechanisms, including the activation of endogenous antioxidant defenses such as Nrf2 and 
suppression of pro-inflammatory transcription factors like NF-κB. Despite promising preclinical evidence 
demonstrating beneficial effects across multiple systems, clinical outcomes have been mixed, with some large trials 
showing limited efficacy of isolated supplementation while others indicate protective effects in combination 
regimens or functional dietary patterns. This review synthesizes current understanding, from molecular 
mechanisms to clinical trials, examining how natural antioxidants influence biological processes and disease 
outcomes, highlighting key challenges, and proposing future research directions.