Leonurine suppresses neuroinflammation through promoting oligodendrocyte maturation
Leonurine suppresses neuroinflammation through promoting oligodendrocyte maturation
复制标题
益母草碱通过促进少突胶质细胞成熟抑制神经炎症
DOI：
10.1111/jcmm.14053
复制
发表时间：
2019-02-01
影响因子：
5.3
通讯作者：
Zhang, Yanyun
中科院分区：
文献类型：
--
作者：
Jin, Min;Li, Qian;Zhang, Yanyun
局灶性炎症和髓鞘再生失败是多发性硬化症及其动物模型实验性自身免疫性脑脊髓炎（EAE）的主要标志。在这项研究中，我们发现益母草碱（一种生物活性生物碱）可以减轻 EAE 疾病的严重程度，同时减少中枢神经系统炎症和髓磷脂损伤。在 EAE 发病过程中，益母草碱显着抑制致脑炎 T 细胞向中枢神经系统的募集，但不会损害外周免疫反应和小胶质细胞激活。从机制上讲，益母草碱通过促进 EAE 和铜宗诱导的脱髓鞘小鼠模型中少突胶质细胞的成熟，保护小鼠免受脱髓鞘，并增强髓鞘再生。此外，我们还发现，经过益母草碱处理后，含有去甲基化酶jumonji结构域的蛋白D3的表达显着增强，从而抑制了组蛋白H3赖氨酸-27的三甲基化，并相应地增强了少突胶质细胞的成熟。总的来说，我们的研究确定了益母草碱对 EAE 模型的治疗作用，这可能代表了多发性硬化症甚至其他脱髓鞘疾病的一种有前途的治疗策略。
Focal inflammation and remyelination failure are major hallmarks of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). In this study, we found that leonurine, a bioactive alkaloid, alleviated EAE disease severity along with reduced central nervous system inflammation and myelin damage. During the pathogenesis of EAE, leonurine dramatically suppressed the recruitment of encephalitogenic T cells into the central nervous system, whereas did not impair periphery immune responses and microglia activation. Mechanistically, leonurine protected mice against demyelination along with enhanced remyelination through promoting the maturation of oligodendrocytes in both EAE and cuprizone‐induced demyelination mouse models. Moreover, we identified that the expression of demethylase jumonji domain‐containing protein D3 was significantly enhanced upon treatment of leonurine, which suppressed the trimethylation of histone H3 lysine‐27 and enhanced oligodendrocyte maturation accordingly. Collectively, our study identified the therapeutic effect of leonurine on EAE model, which potentially represents a promising therapeutic strategy for multiple sclerosis, even other demyelination disorders.