Bioactive Phytochemicals in Experimental Models of Multiple Sclerosis: Mechanisms, Efficacy, and Translational...

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system marked by inflammatory demyelination and progressive neurodegeneration. Although current immunomodulatory therapies can reduce relapse rates, they are often associated with limited long-term efficacy and adverse effects, highlighting the need for safer and more comprehensive complementary approaches. Dietary bioactive phytochemicals-notably, the polyphenols epigallocatechin-3-gallate (EGCG), curcumin, and resveratrol-have demonstrated potential to modulate the immune and inflammatory pathways implicated in MS pathogenesis. In addition to their immunomodulatory roles, emerging evidence suggests that these compounds also exert neuroprotective effects independent of immune modulation, including antioxidant activity, mitochondrial stabilization, and enhancement of neurotrophic signaling. Furthermore, recent studies identify the gut microbiota as a central mediator of MS pathophysiology and of how dietary phytochemicals are metabolized and exert their effects. This review examines experimental data evaluating the therapeutic potential of selected bioactive phytochemicals in MS, focusing on their mechanisms of action-including both immune-dependent and immune-independent neuroprotective effects-and interactions with the gut microbiota. Current limitations in translating findings from animal models to clinical settings are also discussed, and future directions for research in this evolving area are highlighted.