Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-γ/ROR-γt Signaling

被引:0
作者
Wen Li
Zhihui Zhang
Kai Zhang
Zhenyi Xue
Yan Li
Zimu Zhang
Lijuan Zhang
Chao Gu
Qi Zhang
Junwei Hao
Yurong Da
Zhi Yao
Ying Kong
Rongxin Zhang
机构
[1] Tianjin Medical University,Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseas
[2] Tianjin Medical University General Hospital,Department of Neurology, Tianjin Neurological Institute
[3] Dalian Medical University,Department of Biochemistry and Molecular
来源
Molecular Neurobiology | 2016年 / 53卷
关键词
Arctigenin; Th17 cells; Experimental autoimmune encephalomyelitis; AMPK; PPAR-γ;
D O I
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学科分类号
摘要
Arctigenin is a herb compound extract from Arctium lappa and is reported to exhibit pharmacological properties, including neuronal protection and antidiabetic, antitumor, and antioxidant properties. However, the effects of arctigenin on autoimmune inflammatory diseases of the CNS, multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis (EAE) are still unclear. In this study, we demonstrated that arctigenin-treated mice are resistant to EAE; the clinical scores of arctigenin-treated mice are significantly reduced. Histochemical assays of spinal cord sections also showed that arctigenin reduces inflammation and demyelination in mice with EAE. Furthermore, the Th1 and Th17 cells in peripheral immune organs are inhibited by arctigenin in vivo. In addition, the Th1 cytokine IFN-γ and transcription factor T-bet, as well as the Th17 cytokines IL-17A, IL-17F, and transcription factor ROR-γt are significantly suppressed upon arctigenin treatment in vitro and in vivo. Interestedly, Th17 cells are obviously inhibited in CNS of mice with EAE, while Th1 cells do not significantly change. Besides, arctigenin significantly restrains the differentiation of Th17 cells. We further demonstrate that arctigenin activates AMPK and inhibits phosphorylated p38, in addition, upregulates PPAR-γ, and finally suppresses ROR-γt. These findings suggest that arctigenin may have anti-inflammatory and immunosuppressive properties via inhibiting Th17 cells, indicating that it could be a potential therapeutic drug for multiple sclerosis or other autoimmune inflammatory diseases.
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页码:5356 / 5366
页数:10
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