Astragalosides from Radix Astragali benefits experimental autoimmune encephalomyelitis in C57BL /6 mice at multiple levels

BMC Complementary and Alternative Medicine

Zheng-Tao Wang²  Xiao-Jun Wu²  Wei Dou²  Bei-Bei Zhang²  Hui Wu²  Hong-Shuai Liu²  Fei Huang²  Hai-Lian Shi²  Min Du¹  Yi-Xin He² 

[1] Unit of Immune Signaling and Regulation, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 201203, China;The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

关键词: Apoptosis;    Oxidative stress;    Neuroinflammation;    Multiple sclerosis;    Experimental autoimmune encephalomyelitis;    Astragalosides;   

Others  :  1086897
DOI  :  10.1186/1472-6882-14-313

 received in 2014-04-09, accepted in 2014-08-20,  发布年份 2014

【 摘 要 】

Background

Radix Astragali is famous for its beneficial effect on inflammation associated diseases. This study was to assess the efficacy of astragalosides (AST) extracted from Radix Astragali, on the progression of experimental autoimmune encephalomyelitis (EAE), and explore its possible underlying molecular mechanisms.

Methods

EAE was induced by subcutaneous immunization of MOG_35–55. Infiltration of inflammatory cells was examined by HE staining. ROS level was detected by measuring infiltrated hydroethidine. Leakage of blood brain barrier (BBB) was assessed using Evan’s blue dye extravasation method. Levels of inflammatory cytokines were measured using ELISA kits. Activities of total-SOD, GSH-Px, and iNOS and MDA concentration were measured using biochemical analytic kits. Gene expression was detected using real-time PCR method. Protein expression was assayed using western blotting approach.

Results

AST administration attenuated the progression of EAE in mice remarkably. Further studies manifested that AST treatment inhibited infiltration of inflammatory cells, lessened ROS production and decreased BBB leakage. In peripheral immune-systems, AST up-regulated mRNA expression of transcriptional factors T-bet and Foxp3 but decreased that of RORγt to modulate T cell differentiation. In CNS, AST stopped BBB leakage, reduced ROS production by up-regulation of T-SOD, and reduced neuroinflammation by inhibition of iNOS and other inflammatory cytokines. Moreover, AST inhibited production of p53 and phosphorylation of tau by modulation of the Bcl-2/Bax ratio.

Conclusions

AST orchestrated multiple pathways, including immuno-regulation, anti-oxidative stress, anti-neuroinflammation and anti-neuroapoptosis involved in the MS pathogenesis, to prevent the deterioration of EAE, which paves the way for the application of it in clinical prevention/therapy of MS.

【 授权许可】

   
2014 He et al.; licensee BioMed Central Ltd.

【 图 表 】

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