Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-γ/ROR-γt Signaling
Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-γ/ROR-γt Signaling
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Arctigenin 通过 AMPK 和 PPAR-γ/ROR-γt 信号传导抑制 Th17 细胞并改善实验性自身免疫性脑脊髓炎
DOI：
10.1007/s12035-015-9462-1
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发表时间：
2016-10-01
影响因子：
5.1
通讯作者：
Zhang, Rongxin
中科院分区：
文献类型：
--
作者：
Li, Wen;Zhang, Zhihui;Zhang, Rongxin
牛蒡子苷元是从牛蒡子中提取的一种中药化合物，具有神经保护、抗糖尿病、抗肿瘤和抗氧化等药理作用。然而，牛蒡子苷元对中枢神经系统自身免疫性炎症性疾病、多发性硬化（MS）及其动物模型实验性自身免疫性脑脊髓炎（EAE）的作用尚不清楚。在这项研究中，我们证明了牛蒡苷元治疗的小鼠对EAE有抵抗力;牛蒡苷元治疗的小鼠的临床评分显着降低。脊髓切片的组织化学分析也表明，牛蒡子苷元减少了EAE小鼠的炎症和脱髓鞘。此外，牛蒡子苷元在体内可抑制外周免疫器官中的Th 1和Th 17细胞。此外，牛蒡子苷元在体内外均能显著抑制Th 1细胞因子IFN-γ和转录因子T-bet，以及Th 17细胞因子IL-17 A、IL-17 F和转录因子ROR-γt。牛蒡子苷元对Th 17细胞的分化有明显的抑制作用。我们进一步证明牛蒡子苷元激活AMPK并抑制磷酸化p38，此外，上调PPAR-γ，并最终抑制ROR-γt。这些结果表明牛蒡子苷元可能通过抑制Th 17细胞而具有抗炎和免疫抑制作用，表明其可能是多发性硬化症或其他自身免疫性炎症疾病的潜在治疗药物。
Arctigenin is a herb compound extract fromArctium lappaand 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.