Multiple sclerosis (MS), an autoimmune and degenerative disease, is characterized by
demyelination and chronic
neuroinflammation.
Bixin is a
carotenoid isolated from the seeds of Bixa orellana that exhibits various potent pharmacological activities, including
antioxidant, anti-inflammatory, and anti-
tumor properties. However, the effects of
bixin on MS have not yet been examined. To evaluate the effects and underlying molecular mechanisms of
bixin on MS,
experimental autoimmune encephalomyelitis (EAE) was established in C57BL/6 mice, which were treated via intragastric administration of
bixin solutions. To evaluate the molecular mechanisms of
bixin, quantitative reverse-transcription PCR, western blot, immunohistochemistry, flow cytometry, and
enzyme-linked
immunosorbent assay analyses were performed. We found that
bixin significantly improved the symptoms and pathology in EAE mice, reduced the release of inflammatory
cytokines TNF-α,
IL-6,
IL-8,
IL-17, and IFN-γ, and increased the expression of the anti-inflammatory
cytokine IL-10. And
bixin reduced the proportion of Th1 and Th17 cells in the spleen and CNS, and suppressed microglia aggregation, and TXNIP/NLRP3
inflammasome activity by scavenging excessive
reactive oxygen species (ROS) in EAE mice. Furthermore,
bixin inhibited
inflammation and oxidative stress via activating nuclear factor erythroid 2-related factor 2 (NRF2), and its downstream genes in EAE mice, meanwhile, these effects were suppressed upon treatment with an NRF2 inhibitor, ML385.
Bixin prevented
neuroinflammation and
demyelination in EAE mice primarily by scavenging ROS through activation of the NRF2 signaling pathway. Taken together, our results indicate that
bixin is a promising therapeutic candidate for treatment of MS.