Carotenoids as neuroprotective agents in multiple sclerosis: Pathways, mechanisms, and clinical prospects

Multiple sclerosis (MS) is a chronic autoimmune andneurodegenerative disorder affecting the central nervous system (CNS), characterized by demyelination and neuroinflammatory responses, oxidative stress, and immune dysregulation. The global incidence of MS is rising, demonstrating the necessity for new therapeutic agents against its complex pathophysiology. Carotenoids, naturally pigments with strong antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective activities, have been recognized as promising candidates to target MS.The antioxidant effect of astaxanthin, lycopene, β-carotene, crocin, and lutein resulted from the deactivation of reactive oxygen species (ROS), preservation of mitochondrial integrity, and prevention of lipid peroxidation. Additionally, carotenoids regulate inflammatory pathways by suppressing NF-κB activation, reducing the expression of pro-inflammatory cytokines and activating the antioxidant response of the nuclear factor erythroid 2-related factor 2 (Nrf2) system. Carotenoids promote an immune balance that drives Th1/Th17 responses toward regulatory T cell (Treg)activity and reduces neuroinflammation and protecting oligodendrocytes necessary for the process of remyelination. Moreover, the role of phytochemicals in maintaining blood-brain barrier integrity and modulating gene expression provides evidence for their therapeutic potential.