Immunoregulatory Effect of Curcumin on Experimental Autoimmune Encephalomyelitis (EAE), an Animal Model of Multiple...

Demyelination and progressive neurodegeneration within the central nervous system (CNS) are hallmarks of multiple sclerosis (MS), a chronic autoimmune disease. This review critically assesses the therapeutic efficacy of curcumin-a polyphenolic compound from the rhizome of Curcuma longa turmeric-in experimental autoimmune encephalomyelitis, a well-recognized animal model of MS. The significant anti-inflammatory and antioxidant properties of curcumin help slow the development of EAE. By suppressing pro-inflammatory cytokines, including interleukin-12 (IL-12), interleukin-17 (IL-17), and interferon-gamma (IFN-γ), curcumin mechanistically modifies immune responses while enhancing anti-inflammatory pathways through the upregulation of regulatory T cells (Tregs) and promotion of T helper 2 immune responses. At the same time, it enhances antiinflammatory pathways by upregulating Tregs and promoting T helper 2 (Th2) immune responses. Curcumin also has neuroprotective qualities by increasing the expression of neurotrophic factors, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which promote remyelination and maintain the viability of neurons. In addition, curcumin changes important intracellular signaling pathways, such as the Janus kinase/signal transducer and activator of transcription (JAK/STAT) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, which help to preserve the integrity of the blood-brain barrier (BBB) and reduce oxidative stress. Despite challenges associated with curcumin's bioavailability and pharmacokinetics, innovative delivery systems such as polymerized nano-curcumin and exosome-encapsulated formulations show promise in enhancing its therapeutic efficacy. Curcumin appears to be a promising adjunctive therapy for MS, requiring further clinical research to optimize its application in MS care.