Early astragaloside IV administration attenuates experimental autoimmune encephalomyelitis in mice by suppressing the maturation and function of dendritic cells.

AIMS

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.

MAIN METHODS

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.

KEY FINDINGS

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.

SIGNIFICANCE

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.