1 Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of the Ministry of Education and the Collaborative Innovation Center for Brain Science, Naval Medical University, Shanghai 200433, China 

2 Changhai Stroke Center, Changhai Hospital, Naval Medical University, Shanghai 200433, China 

3 The 983rd Hospital of Joint Logistics Support Forces of the PLA, Tianjin 300142, China 

4 The 988th Hospital of Joint Logistics Support Forces of the PLA, Zhengzhou 450000, China

 

Abstract

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.

 

Keywords

Pinocembrin; Oligodendrocytes; Differentiation; Remyelination; MTOR

 

[SpringerLink]