Fucoxanthin ameliorates experimental autoimmune encephalomyelitis by inhibiting microglial NLRP3 inflammasome.

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) characterized by focal inflammation, demyelination, axonal injury, and neuronal damage. Microglia-mediated neuroinflammation plays a critical role in its pathogenesis. Fucoxanthin (Fx), a compound abundant in various algae, exhibits antioxidant, anti-tumor, and anti-inflammatory properties. This study aimed to investigate the therapeutic effects and underlying mechanisms of Fx in ameliorating experimental autoimmune encephalomyelitis (EAE), a well-established animal model of MS. Our results demonstrated that Fx significantly attenuated inflammatory cell infiltration, demyelination, and activation of pro-inflammatory M1-polarized microglia in the spinal cords of EAE mice. Moreover, we found that Fx exerted anti-inflammatory effects by inhibiting the activation of the NLRP3 inflammasome and subsequent pyroptosis in microglia, both in EAE mice and in BV2 microglial cells. In summary, Fx exhibited a promising therapeutic effect on EAE by suppressing neuroinflammation through inhibition of microglial M1 polarization and NLRP3 inflammasome-mediated pyroptosis. Thus, Fx may represent a potential therapeutic agent for the treatment of MS.