Abstract

Oxidative stress and inflammation are tightly intertwined drivers of acute and chronic disease. Antioxidant 
phytochemicals-plant-derived polyphenols, carotenoids, organosulfur compounds and related small molecules
modulate redox balance and reprogram immune responses through multi-layered mechanisms that extend beyond 
simple radical scavenging. Preclinical models demonstrate that phytochemicals (for example, resveratrol, curcumin, 
quercetin, EGCG, lutein, sulforaphane) regulate Nrf2- and NF-κB-dependent transcription, restrain inflammasome 
activation, alter kinase signaling (MAPK, JAK-STAT), shape immune cell metabolism and epigenetics, and interact 
with the gut microbiome to generate bioactive metabolites. Clinical translation has produced promising biomarker 
changes and condition-specific benefits, but large-scale, consistent clinical efficacy is limited by low oral 
bioavailability, heterogenous formulations, variable dosing, and incomplete mechanistic bridging (PK–PD). This 
review synthesizes current mechanistic and translational evidence, highlights clinical studies and limitations, and 
proposes priorities standardized preparations, PK–PD mapping, targeted patient selection, and microbiome-aware 
strategies to move antioxidant phytochemicals from bench to bedside.