Go-sha-jinki-Gan Alleviates Inflammation in Neurological Disorders via p38-TNF Signaling in the Central Nervous System
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ORIGINAL ARTICLE
Go-sha-jinki-Gan Alleviates Inflammation in Neurological Disorders via p38-TNF Signaling in the Central Nervous System Shiying Jiang 1 & Kousuke Baba 1 & Tatsusada Okuno 1 & Makoto Kinoshita 1 & Chi-Jing Choong 1 & Hideki Hayakawa 1 & Hiroshi Sakiyama 1 & Kensuke Ikenaka 1 & Seiichi Nagano 1 & Tsutomu Sasaki 1 & Munehisa Shimamura 1,2 & Yoshitaka Nagai 1,3 & Keisuke Hagihara 4 & Hideki Mochizuki 1 Accepted: 7 October 2020 # The American Society for Experimental NeuroTherapeutics, Inc. 2020
Abstract 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. Key Words Go-sha-jinki-Gan . inflammation . multiple sclerosis . 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine . tumor necrosis factor-α . p38
Shiying Jiang, Kousuke Baba contributed equally as first authors; Keisuke Hagihara, Hideki Mochizuki contributed equally as corresponding authors to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13311-020-00948-w) contains supplementary material, which is available to authorized users. * Keisuke Hagihara [email protected] * Hideki Mochizuki [email protected] 1
Department of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
2
Department of Health Development and Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
3
Department of Neurotherapeutics, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
4
Department of Advanced Hybrid Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
Introduction Traditional Oriental herbal medicine is increasingly used worldwide. Go-
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