Signaling pathways driving multiple sclerosis: From mechanisms to natural‑product interventions

Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disorder of the central nervous system characterized by inflammation and progressive neurodegeneration. MS is a heterogeneous disease with varying presentations, disease courses, and prognosis. Although current disease-modifying therapies (DMTs) have been reported to reduce the frequency and severity of inflammatory demyelinating hallmarks of MS, improve relapse rate and long-term outcomes, they do not fully prevent disease progression, nor do they reverse existing neurological damage. This ongoing gap has driven growing interest in natural products as complementary or adjunctive strategies for MS management. Naturally occurring phytochemicals have been proposed as a potentially safe and effective therapeutic and complementary option for MS. Natural compounds have been reported to demonstrate anti-inflammatory, immunomodulatory, antioxidant, and neuroprotective activities in experimental models of MS. Together, these multifunctional properties target key mechanistic pathways implicated in disease pathogenesis, such as oxidative stress, mitochondrial dysfunction, and immune dysregulation. However, despite promising preclinical data, clinical translation remains limited by variability in dosing, bioavailability challenges, and insufficient large-scale trials. In this context, this review explores the scientific rationale for natural products in MS, provides an overview of disease mechanisms relevant to such interventions, and highlights future research needs to advance these compounds toward evidence-based integration.