Abstract

Phytochemical antioxidants, encompassing diverse plant-derived molecules such as polyphenols, carotenoids, 
organosulfur compounds, and certain alkaloids, represent a crucial interface between diet and immune system 
regulation. While their early recognition centered on the ability to neutralize reactive oxygen species (ROS), 
contemporary evidence highlights far broader immunological roles. These compounds modulate redox-sensitive 
transcription factors such as Nrf2, enhance endogenous antioxidant defense, and suppress pro-inflammatory 
programs mediated by NF-κB. They further influence MAPK and JAK-STAT pathways, restrict inflammasome 
activation, and engage in bidirectional interactions with the gut microbiota, ultimately shaping both innate and 
adaptive immune responses. Preclinical data provide consistent mechanistic insights, demonstrating that compounds 
such as resveratrol, curcumin, quercetin, epigallocatechin gallate (EGCG), and lutein regulate cytokine production, 
macrophage polarization, and T cell differentiation. However, translating these findings into consistent clinical 
outcomes remains challenging due to low bioavailability, variable dosing regimens, pleiotropic biological effects, and 
heterogeneous clinical trial designs. This review therefore synthesizes mechanistic evidence, critically evaluates 
clinical data, and addresses pharmacokinetic, formulation, and safety considerations. It further outlines research 
priorities aimed at bridging laboratory discoveries with therapeutic applications, emphasizing the translational 
potential of phytochemical antioxidants as adjuncts in immune modulation and disease prevention.