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.
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.
Subject(s)
Animals , Mice , Rats , Cell Differentiation , Flavanones , Mice, Inbred C57BL , Myelin Sheath/metabolism , Oligodendroglia/metabolism , Remyelination , Signal Transduction , TOR Serine-Threonine Kinases/metabolismABSTRACT
Objective To analyze the different metabolites of the classical activated (M1) ,alternatively activated (M2) and resting BV2 cells by metabolomics method .Methods The mRNAs of several potential biomarkers were determined by real-time PCR analyses to confirm the state of BV2 cells .Static GC-MS combined with metabolomics technology was used to analyze the metabolic changes .Results There were 15 biomarkers identified between the M1 group and the resting group ,and 15 biomarkers were found in the M2 group and the resting group .Conclusion The present study provides an effective way to reveal the mechanism of the polarization of BV 2 cell ,and it might provide a theoretical basis to prevent or treat the neurodegen-erative diseases .