title: Moringin activates Wnt canonical pathway by inhibiting GSK3β in a mouse model of experimental autoimmune encephalomyelitis.
abstract: 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.
authors: IRCCS Centre Neurolesi "Bonino-Pulejo", Messina, Italy.
authors: Sabrina
authors: S
authors: Giacoppo
authors: IRCCS Centre Neurolesi "Bonino-Pulejo", Messina, Italy.
authors: Thangavelu
authors: T
authors: Soundara Rajan
authors: Council for Agricultural Research and Economics, Research Centre for Industrial Crops (CREA-CIN), Bologna, Italy.
authors: Gina Rosalinda
authors: GR
authors: De Nicola
authors: Council for Agricultural Research and Economics, Research Centre for Industrial Crops (CREA-CIN), Bologna, Italy.
authors: Renato
authors: R
authors: Iori
authors: IRCCS Centre Neurolesi "Bonino-Pulejo", Messina, Italy.
authors: Placido
authors: P
authors: Bramanti
authors: IRCCS Centre Neurolesi "Bonino-Pulejo", Messina, Italy.
authors: Emanuela
authors: E
authors: Mazzon
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017879:Isothiocyanates / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D017879:Isothiocyanates; C000614007:moringin; D000071679:Glycogen Synthase Kinase 3 beta
keywords: GSK3β; PPARγ; Wnt–β-catenin pathway; apoptosis; moringin; multiple sclerosis