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.

进行性多发性硬化症（MS）的恶化与少突胶质祖细胞（OPCs）的分化受阻密切相关。为了发现通过内源性 OPCs 增强髓鞘再生的新型治疗化合物，我们使用培养的大鼠 OPCs 和小分子化合物库筛选了髓鞘碱性蛋白的表达。最有效的药物之一是松松素，它显着促进 OPC 分化和成熟，而不影响细胞增殖和存活。基于这些体外我们进一步评估了松松素在脱髓鞘疾病动物模型中的治疗作用。我们证明松松素显着改善了实验性自身免疫性脑脊髓炎 (EAE) 的进展，并增强了溶血凝集素诱导病变中脱髓鞘的修复。进一步的研究表明，松木素增加了哺乳动物雷帕霉素靶蛋白 (mTOR) 的磷酸化水平。总之，我们的研究结果表明，松松素通过磷酸化的 mTOR 途径促进 OPC 分化和髓鞘再生，并为这种天然类黄酮产品治疗脱髓鞘疾病提供了新的治疗前景。