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 Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, Tianjin, 300070, China.
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Mol Neurobiol. 2016 Oct;53(8):5356-66. doi: 10.1007/s12035-015-9462-1. Epub 2015 Oct 6.
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.
牛蒡子苷元是一种从牛蒡中提取的植物化合物，据报道具有多种药理作用，包括神经元保护作用以及抗糖尿病、抗肿瘤和抗氧化作用。然而，牛蒡子苷元对中枢神经系统自身免疫性炎症性疾病、多发性硬化症（MS）及其动物模型实验性自身免疫性脑脊髓炎（EAE）的影响尚不清楚。在本研究中，我们证明了牛蒡子苷元处理的小鼠对 EAE 具有抗性；牛蒡子苷元处理的小鼠的临床评分显著降低。脊髓切片的组织化学分析也表明，牛蒡子苷元减轻了 EAE 小鼠的炎症和脱髓鞘。此外，牛蒡子苷元在体内抑制了外周免疫器官中的 Th1 和 Th17 细胞。此外，Th1 细胞因子 IFN-γ 和转录因子 T-bet 以及 Th17 细胞因子 IL-17A、IL-17F 和转录因子 ROR-γt 在体外和体内经牛蒡子苷元处理后均受到显著抑制。有趣的是，EAE 小鼠的中枢神经系统中 Th17 细胞明显受到抑制，而 Th1 细胞没有明显变化。此外，牛蒡子苷元明显抑制 Th17 细胞的分化。我们进一步证明，牛蒡子苷元通过激活 AMPK 并抑制磷酸化 p38，上调 PPAR-γ，最终抑制 ROR-γt，从而发挥抗炎和免疫抑制作用。这些发现表明，牛蒡子苷元可能通过抑制 Th17 细胞发挥抗炎和免疫抑制作用，表明它可能成为多发性硬化症或其他自身免疫性炎症性疾病的潜在治疗药物。
