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-α (TNF-α) 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-α 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-α via p38-TNF signaling.

Go-sha-jinki-Gan (GJG) 是一种传统的日本草药。在临床实践中，GJG 对化疗或糖尿病引起的神经性疼痛和超敏反应有效。在我们之前使用慢性收缩损伤小鼠模型的研究中，我们发现 GJG 通过抑制外周神经系统中肿瘤坏死因子-α (TNF-α) 和 p38 丝裂原活化蛋白激酶 (p38 MAPK) 的表达来抑制小胶质细胞的活化. 为了研究 GJG 是否可以在神经系统疾病的背景下抑制中枢神经系统 (CNS) 的炎症，我们检查了 GJG 对两种神经系统疾病小鼠模型中常驻神经胶质细胞激活和 p38-TNF 信号传导的影响：多发性硬化和 1-methyl-4-phenyl-1,2,3 的实验性自身免疫性脑脊髓炎 (EAE) 模型，帕金森病的 6-四氢吡啶 (MPTP) 模型。GJG 给药通过减少 EAE 小鼠脊髓和 MPTP 治疗小鼠的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。我们得出结论，GJG 通过抑制神经胶质细胞活化来减轻 CNS 的炎症，然后通过 p38-TNF 信号传导减少 TNF-α 的产生。GJG 抑制了这两种小鼠模型的神经胶质细胞中 p38 的磷酸化。我们得出结论，GJG 通过抑制神经胶质细胞活化来减轻 CNS 的炎症，然后通过 p38-TNF 信号传导减少 TNF-α 的产生。GJG 抑制了这两种小鼠模型的神经胶质细胞中 p38 的磷酸化。我们得出结论，GJG 通过抑制神经胶质细胞活化来减轻 CNS 的炎症，然后通过 p38-TNF 信号传导减少 TNF-α 的产生。