Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
2011 Collaborative Innovation Center/Research Center of Neurobiology, University of Shanxi Traditional Chinese Medicine, Taiyuan, Shanxi, China.
Int Immunopharmacol. 2019 May;70:284-294. doi: 10.1016/j.intimp.2019.02.035. Epub 2019 Mar 6.
Multiple sclerosis is a T cell-mediated inflammatory, demyelinating disease of the central nervous system, accompanied by neuronal degeneration. Based on the anti-inflammatory effects of Ginkgolide K (GK), a platelet activating factor antagonist, we explored the possible application of GK in the treatment of MS. The results showed that GK effectively ameliorated the severity of experimental autoimmune encephalomyelitis. The intervention of GK inhibited the infiltration of inflammatory cells and demyelination in the spinal cord. At the same time, the expression of the inflammation-related molecules TLR4, NF-κB, and COX2 in the spinal cord was significantly lower in the GK-treated mice, indicating that GK intervention can inhibit the inflammatory microenvironment of the spinal cord in EAE mice. In mouse spleen lymphocytes, GK increased the proportion of regulatory T cells (Treg) and reduced the proportion of T helper 17 cells (Th17), modifying the imbalance between Th17/Treg cells. Additionally, GK shifted macrophage/microglia polarization from M1 to M2 cell type. Importantly, GK inhibited the expression of chemotactic molecules CCL-2, CCL-3 and CCL-5, thereby limiting the migration of inflammatory cells to the spinal cord. Our results provide the possibility that GK may be a promising naturally small molecule compound for the future treatment of MS.
多发性硬化症是一种 T 细胞介导的中枢神经系统炎症性脱髓鞘疾病，伴有神经元变性。基于血小板激活因子拮抗剂白果内酯 K（GK）的抗炎作用，我们探讨了 GK 在多发性硬化症治疗中的可能应用。结果表明，GK 可有效改善实验性自身免疫性脑脊髓炎的严重程度。GK 的干预抑制了脊髓中炎症细胞的浸润和脱髓鞘。同时，GK 处理的小鼠脊髓中与炎症相关的分子 TLR4、NF-κB 和 COX2 的表达显著降低，表明 GK 干预可抑制 EAE 小鼠脊髓的炎症微环境。在小鼠脾淋巴细胞中，GK 增加了调节性 T 细胞（Treg）的比例，降低了辅助性 T 细胞 17 细胞（Th17）的比例，纠正了 Th17/Treg 细胞的失衡。此外，GK 将巨噬细胞/小胶质细胞的极化从 M1 型转变为 M2 型。重要的是，GK 抑制趋化因子 CCL-2、CCL-3 和 CCL-5 的表达，从而限制了炎症细胞向脊髓的迁移。我们的结果提供了一种可能性，即 GK 可能是一种有前途的天然小分子化合物，用于未来多发性硬化症的治疗。
