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While T lymphocytes have long been regarded as central to MS pathogenesis, accumulating evidence underscores the pivotal role of B lymphocytes and dysregulated cytokine networks (e.g., Th17\/IL\u201017 and NF\u2010\u03baB pathways) in driving disease initiation and progression. Despite advances in symptomatic management and disease\u2010modifying therapies (DMTs), clinical interventions for MS remain constrained by severe side effects, drug dependency, and suboptimal long\u2010term efficacy, highlighting an urgent unmet need for novel therapeutic strategies. Natural compounds (e.g., alkaloids, flavonoids, terpenoids, and polyphenols) have emerged as promising candidates owing to their inherent biocompatibility, favorable safety profiles, and multi\u2010targeted regulatory effects on neuroinflammation. This review critically synthesizes and evaluates current evidence on the therapeutic potential of natural compounds in MS, with a focus on cross\u2010compound class integration of core common pathways (e.g., NF\u2010\u03baB inhibition and Th17\/Treg balance modulation) rather than isolated mechanism descriptions. We explicitly compare the strength of evidence across different natural compounds, clarifying which findings are well\u2010substantiated versus preliminary. Notably, we emphasize the inherent limitations of experimental autoimmune encephalomyelitis (EAE) models in recapitulating human MS pathophysiology (e.g., interspecies immune divergence and disease heterogeneity) and integrate or at least reference relevant clinical\/epidemiological evidence to enhance translational relevance. Finally, we outline key future perspectives, including the integration of natural products with existing DMTs, challenges in clinical trial design, and prospects of combination therapies, aiming to provide a directional framework for advancing natural compounds from preclinical exploration to actionable clinical therapeutic targets in MS and enhancing the translational impact of this field.<\/jats:p>","DOI":"10.1155\/jimr\/6333512","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:22:16Z","timestamp":1774531336000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["From Demyelination to Intervention: Natural Compounds as Emerging Therapeutic Targets in Multiple Sclerosis 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