The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Taiyuan 030024, China.
The First Clinical College, Shanxi Medical University, Taiyuan 030001, China.
Int Immunopharmacol. 2019 Jan;66:69-81. doi: 10.1016/j.intimp.2018.09.041. Epub 2018 Nov 13.
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by recurrent and progressive demyelination, neuroinflammation and oligodendrocyte loss. The cuprizone (CPZ) model is characterized by primary and reversible demyelination, accompanied by oligodendrocyte loss and neuroinflammation. In the current study, we explored the efficiency of Bilobalide in the demyelination and remyelination. The results demonstrate that Bilobalide improved behavioral abnormality and promoted remyelination in the corpus callosum by using Luxol Fast Blue, Black Gold II and myelin basic protein (MBP) staining. We for the first time found that CPZ caused the splenic atrophy and induced the formation of myelin oligodendrocyte glycoprotein (MOG) antibody, which was attenuated by Bilobalide. Thus, Bilobalide decreased the loss of O4+ oligodendrocytes possibly through MOG antibody-dependent cell cytotoxicity. Bilobalide also prevented the infiltration of CD4 T cells, CD68 macrophages and B220 B cells within the brain, and reduced the inflammatory microenvironment mediated with Iba1iNOS and Iba1NF-kB microglia after CPZ challenge, accompanied by the inhibition of IL-1β and IL-6 in the brain. These results identify a potent therapeutic efficiency for Bilobalide and highlight clear pleiotropic effects of the compound beyond specific autoantibody and inflammatory microenvironment in CPZ-mediated demyelination.
多发性硬化症（MS）是一种中枢神经系统的慢性脱髓鞘疾病，其特征是复发性和进行性脱髓鞘、神经炎症和少突胶质细胞丧失。铜锌齐（CPZ）模型的特征是原发性和可逆性脱髓鞘，伴有少突胶质细胞丧失和神经炎症。在本研究中，我们探讨了白果内酯在脱髓鞘和髓鞘再生中的效率。结果表明，白果内酯通过使用卢索快速蓝、黑金 II 和髓鞘碱性蛋白（MBP）染色，改善了胼胝体中的行为异常，并促进了髓鞘再生。我们首次发现 CPZ 导致脾脏萎缩，并诱导髓鞘少突胶质细胞糖蛋白（MOG）抗体的形成，而白果内酯可以减弱这种作用。因此，白果内酯通过 MOG 抗体依赖性细胞毒性减少了 O4+少突胶质细胞的损失。白果内酯还可以防止 CPZ 攻击后大脑内 CD4 T 细胞、CD68 巨噬细胞和 B220 B 细胞的浸润，并降低由 Iba1iNOS 和 Iba1NF-kB 小胶质细胞介导的炎症微环境，同时抑制大脑中的 IL-1β 和 IL-6。这些结果表明白果内酯具有很强的治疗效果，并强调了该化合物在 CPZ 介导的脱髓鞘中除了特定自身抗体和炎症微环境之外的明显多效性作用。
