Aberrant canonical Wnt-β-
catenin signaling has been reported in
multiple sclerosis (MS), although the results are controversial. The present study aimed to examine the role of the Wnt-β-
catenin pathway in experimental MS and also to test
moringin (4-[α-L-rhamnopyranosyloxy]-
benzyl isothiocyanate), resulting from exogenous
myrosinase hydrolysis of the natural
phytochemical glucomoringin 4(α-L-rhamnosyloxy)-benzyl
glucosinolate as a modulator of
neuroinflammation via the β-
catenin-PPARγ axis.
Experimental autoimmune encephalomyelitis (EAE), the most common model of MS, was induced in C57BL/6 mice by immunization with MOG35-55. Released
moringin (10 mg/kg glucomoringin +5 μL
myrosinase/mouse) was administered daily for 1 week before EAE induction and continued until mice were killed on day 28 after EAE induction. Our results clearly showed that the Wnt-β-
catenin pathway was downregulated in the EAE model, whereas
moringin pretreatment was able to avert this.
Moringin pretreatment normalizes the aberrant Wnt-β-
catenin pathway, resulting in GSK3β inhibition and β-
catenin upregulation, which regulates T-cell activation (CD4 and FoxP3), suppresses the main inflammatory mediators (IL-1β, IL-6, and COX2), through activation of PPARγ. In addition,
moringin attenuates apoptosis by reducing the expression of the
Fas ligand and cleaved
caspase 9, and in parallel increases
antioxidant Nrf2 expression in EAE mice. Taken together, our results provide an interesting discovery in identifying
moringin as a modulator of the Wnt-β-
catenin signaling cascade and as a new potential therapeutic target for MS treatment.