Abstract
It is increasingly recognized that redox injury, one of the most extensively studied processes in disease pathophysiology, pharmacology, and toxicology, is rarely explained by an indiscriminate excess of free radicals alone, but rather by a combination of macromolecular injury, maladaptive redox signaling, ferroptosis, and dysregulated inflammation and metabolism. This paradigm shift has revealed several limitations of traditional antioxidants, including a focus on scavenging effects, poor target engagement, unfavorable or uncertain pharmacokinetics, failure to reach specific subcellular compartments, and lack of robust biomarkers of response. Concomitantly, greater attention is currently being paid to natural compounds combining antioxidant, anti-inflammatory, and metabolic effects. Fucoidans, structurally diverse, fucose-rich, sulfated polysaccharides derived mainly from brown seaweeds, are emerging as promising candidates because they target multiple pathways relevant to oxidative injury, including activation of antioxidant systems, preservation of mitochondrial function, attenuation of ferroptosis, and modulation of gut-organ axes that amplify oxidative tissue damage. This review critically appraises studies conducted over the last ten years, with particular emphasis on newly identified mechanisms, quality of fucoidan characterization, disease-model relevance, and translational potential. Current evidence supports an antioxidant effect of fucoidans, particularly in diseases affecting the liver, kidneys, intestines, central nervous system, and skin/wound healing. However, translation is constrained by heterogeneity across source species, extraction, purification, molecular weight, and analytical reporting. Standardized chemistry, robust pharmacokinetic characterization, and comprehensive assessments of biomarkers of response and organ biology are required to validate the role of fucoidans in mitigating oxidative stress.