Go-sha-jinki-Gan Alleviates Inflammation in Neurological Disorders via p38-TNF Signaling in the Central Nervous System
Go-sha-jinki-Gan Alleviates Inflammation in Neurological Disorders via p38-TNF Signaling in the Central Nervous System
复制标题
DOI：
10.1007/s13311-020-00948-w
复制
发表时间：
2020-10-20
影响因子：
5.7
通讯作者：
Mochizuki, Hideki
中科院分区：
文献类型：
--
作者：
Jiang, Shiying;Baba, Kousuke;Mochizuki, Hideki
Go-sha-jinki-Gan (GJG) 是一种传统的日本草药。在临床实践中，GJG 可有效对抗化疗或糖尿病引起的神经性疼痛和超敏反应。在我们之前使用慢性压迫性损伤小鼠模型的研究中，我们发现GJG通过抑制周围神经系统中肿瘤坏死因子-α（TNF-α）和p38丝裂原激活蛋白激酶（p38 MAPK）的表达来抑制小胶质细胞活化。为了研究 GJG 是否可以在神经系统疾病的情况下抑制中枢神经系统 (CNS) 的炎症，我们在两种神经系统疾病小鼠模型中检查了 GJG 对驻留神经胶质细胞的激活和 p38-TNF 信号转导的影响：多发性硬化症的实验性自身免疫性脑脊髓炎 (EAE) 模型和多发性硬化症的 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 模型帕金森病。 GJG 给药通过减少 EAE 小鼠脊髓和 MPTP 治疗小鼠黑质中小胶质细胞的数量和 TNF-α 的产生，减轻了临床 EAE 症状和 MPTP 诱导的炎症的严重程度。因此，GJG 抑制了这两种小鼠模型的神经胶质细胞中 p38 的磷酸化。我们得出的结论是，GJG 通过抑制神经胶质细胞活化来减轻 CNS 炎症，然后通过 p38-TNF 信号传导减少 TNF-α 的产生。
Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine. In clinical practice, GJG is effective against neuropathic pain and hypersensitivity induced by chemotherapy or diabetes. In our previous study using a chronic constriction injury mouse model, we showed that GJG inhibited microglia activation by suppressing the expression of tumor necrosis factor-alpha (TNF-alpha) and p38 mitogen-activated protein kinase (p38 MAPK) in the peripheral nervous system. To investigate whether GJG can suppress inflammation in the central nervous system (CNS) in the context of neurological disorders, we examined the effect of GJG on the activation of resident glial cells and on p38-TNF signaling in two mouse models of neurological disorders: the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. GJG administration relieved the severity of clinical EAE symptoms and MPTP-induced inflammation by decreasing the number of microglia and the production of TNF-alpha in the spinal cord of EAE mice and the substantia nigra of MPTP-treated mice. Accordingly, GJG suppressed the phosphorylation of p38 in glial cells of these two mouse models. We conclude that GJG attenuates inflammation of the CNS by suppressing glial cell activation, followed by a decrease in the production of TNF-alpha via p38-TNF signaling.