title: Astragalosides from Radix Astragali benefits experimental autoimmune encephalomyelitis in C57BL /6 mice at multiple levels.
abstract: 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 MOG35-55. 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.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: He
authors.forename: Min
authors.initials: M
authors.lastname: Du
authors.forename: Hai-Lian
authors.initials: HL
authors.lastname: Shi
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
authors.forename: Hong-Shuai
authors.initials: HS
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Dou
authors.affiliation: Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210009, China. xiaojunwu320@126.com.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Wu
authors.forename: Zheng-Tao
authors.initials: ZT
authors.lastname: Wang
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D018450:Disease Progression; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D018517:Plant Roots / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D004365:Drugs, Chinese Herbal; D016159:Tumor Suppressor Protein p53