Title:The Protective Effect of Astragalus Polysaccharide on Experimental Autoimmune Encephalomyelitis in Mice by Activating the AMPK/JAK/ STAT3/Arginase-1 Signaling Pathway
Volume: 26
Issue: 6
Author(s): Jin-Li Wang, Bin Li, Xue-Xin He, Chang-Yu Gao, Jue-Qiong Wang, Ruo-Yi Guo, Jing-Yi Fan, Ya-Nan Zhang, Mo-Yuan Quan, Shuang Song and Tao Xie*
Affiliation:
- Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050051, Hebei, China
- Department of Neurology, The Second Hospital of Hebei Medical University, Key Laboratory of Hebei Neurology, Shijiazhuang,
050051, Hebei, China
Keywords:
Multiple sclerosis, Astragalus polysaccharide, experimental autoimmune encephalomyelitis, marrow-derived suppressor cells, Arginase-1, AMPK.
Abstract:
Objective: This study aimed to investigate the protective effect and mechanism of
Astragalus polysaccharide (APS) on autoimmune encephalomyelitis.
Methods: C57BL/6 mice were randomly divided into the blank control group, EAE group, and
APS intervention group (n=15/group). The Experimental Autoimmune Encephalomyelitis (EAE)
mouse model was established by active immunization. The pathological changes in the spinal
cord were evaluated by Hematoxylin-eosin (HE) and Luxol Fast Blue (LFB) staining. The number
of CD11b+ Gr-1+ myeloid-derived suppressor cells (MDSCs) in the spleen tissues of mice in
each group was determined by immunofluorescence staining. The expression of Arginase-1 in
the spinal cord and spleen of each group was detected by immunofluorescence double staining.
The TNF-α, IL-6, and Arginase-1 levels in the spleen were detected by ELISA assay. A western
blot was used to detect the protein expression of the AMPK/JAK/STAT3/Arginase-1 signaling
pathway.
Results: After the intervention of APS, the incidence of autoimmune encephalomyelitis in mice
of the APS group was significantly lower than that in the EAE group, and the intervention of
APS could significantly delay the onset time in the EAE mice, and the score of neurological
function deficit in mice was significantly lower than that in EAE group (P < 0.05). APS intervention
could reduce myelin loss and improve the inflammatory response of EAE mice. Moreover,
it could induce the expression of CD11b+ GR-1 + bone MDSCs in the spleen and increase
the expression of Arginase-1 in the spinal cord and spleen. This study further demonstrated that
APS can protect EAE mice by activating the AMPK/JAK/STAT3/Arginase-1 signaling pathway.
Conclusion: After the intervention of APS, myelin loss and inflammatory response of EAE mice
were effectively controlled. APS promoted the secretion of Arginase-1 by activating MDSCs and
inhibited CD4+T cells by activating AMPK/JAK/STAT3/Arginase-1 signaling pathway, thus
improving the clinical symptoms and disease progression of EAE mice.
