Matrine inhibits the Wnt3a/β-catenin/TCF7L2 signaling pathway in experimental autoimmune encephalomyelitis

Oligodendrocyte (OL) death and remyelination failure lead to progressive neurological deficits in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Matrine (MAT), a quinolizidine alkaloid component derived from the root of Sophora flavescens, has the capacity to effectively inhibit central nervous system (CNS) inflammation and to promote neuroregeneration. In the present study we explored its regulatory mechanism on the Wnt/β-catenin/TCF7L2 pathway, a negative modulator for myelination, in MOG35‐–55 peptide-induced EAE. Our results clearly indicate that MAT treatment reduced the activation of Wnt3a and β-catenin in the CNS of EAE mice, accompanied by the activation of GSK3β and decreased expression of cyclin D1 and Axin2, two target genes of the Wnt3a/β-catenin pathway. In addition, MAT increased OL maturation and myelination, as evidenced by the decreased number of NG2+Olig2+ cells and the increased numbers of MBP+ and CC1+Olig2+ cells. Taken together, these findings indicate that MAT treatment promoted the maturation of OLs and myelin repair, which is closely related to the modulation of the Wnt/β-catenin/TCF7L2 signaling pathway. •Inhibition of differentiation and maturation of oligodendrocytes occurs significantly in the hippocampus and cerebral cortex of experimental autoimmune encephalomyelitis mice.•Matrine can alleviate the symptoms and demyelination of experimental autoimmune encephalomyelitis mice.•Matrine exerts therapeutic effects by inhibiting the activation of Wnt3a/β-catenin/TCF7L2 signaling pathway.•GSK3β participates in the regulation of Wnt signaling pathway.