Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Classical Prescription Experimental Platform, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Life Sci. 2020 May 15;249:117448. doi: 10.1016/j.lfs.2020.117448. Epub 2020 Feb 19.
Dendritic cells (DCs) actively participate in the pathogenesis of multiple sclerosis (MS), an autoimmune disease. Astragaloside IV (ASI), an active monomer isolated from the Chinese medicine Astragalus membranaceus, has a wide range of pharmacological effects. We aimed to elucidate the effects of ASI on the development of DCs in the early stage of MS/EAE.
The mice were administered with ASI (20 mg/kg) daily 3 days in advance of EAE induction and continuously until day 7 post-immunization. The effect of ASI on CD11c DC cells from bone marrow (BMDCs) or the spleen of EAE mice at day 7 post-immunization were investigated respectively by flow cytometry, ELISA, western blot, real-time PCR and immunofluorescence.
ASI administration in the early stage of EAE was demonstrated to delay the onset and alleviate the severity of the disease. ASI inhibited the maturation and the antigen presentation of DCs in spleen of EAE mice and LPS-stimulated BMDCs, as evidenced by decreased expressions of CD11c, CD86, CD40 and MHC II. Accordingly, DCs treated by ASI secreted less IL-6 and IL-12, and prevented the differentiation of CD4 T cells into Th1 and Th17 cells, which was probably through inhibiting the activation of NFκB and MAPKs signaling pathways.
Our results implicated the alleviative effect of early ASI administration on EAE might be mediated by suppressing the maturation and function of DCs. The novel findings may add to our knowledge of ASI in the potentially clinical treatment of MS.
树突状细胞（DCs）在多发性硬化症（MS）这一自身免疫性疾病的发病机制中起积极作用。黄芪甲苷（ASI）是从中药黄芪中分离出的一种活性单体，具有广泛的药理作用。本研究旨在探讨 ASI 对 MS/EAE 早期 DC 发育的影响。
在 EAE 诱导前 3 天开始每天给小鼠服用 ASI（20mg/kg），并持续至免疫后 7 天。通过流式细胞术、ELISA、western blot、实时 PCR 和免疫荧光分别检测 ASI 对免疫后第 7 天 EAE 小鼠骨髓（BMDCs）或脾脏中 CD11c DC 细胞的影响。
在 EAE 的早期阶段给予 ASI 治疗可延迟疾病的发生并减轻其严重程度。ASI 抑制了 EAE 小鼠脾脏和 LPS 刺激的 BMDCs 中 DC 的成熟和抗原呈递，表现在 CD11c、CD86、CD40 和 MHC II 的表达减少。相应地，ASI 处理的 DC 分泌的 IL-6 和 IL-12 减少，并阻止 CD4 T 细胞向 Th1 和 Th17 细胞分化，这可能是通过抑制 NFκB 和 MAPKs 信号通路的激活来实现的。
我们的研究结果表明，早期 ASI 治疗对 EAE 的缓解作用可能是通过抑制 DC 的成熟和功能来介导的。这些新发现可能为我们提供关于 ASI 治疗 MS 的潜在临床应用的新认识。
