title: Astragaloside IV attenuates inflammatory reaction via activating immune function of regulatory T-cells inhibited by HMGB1 in mice.
abstract: BACKGROUND
  High-mobility group box 1 (HMGB1) protein is a highly abundant protein that can promote the pathogenesis of inflammatory. Some experiments have demonstrated a vital role for HMGB1 to modulate the immune function of regulatory T-cells (Tregs). Astragaloside IV (AST IV), an extract from Astragalus membranaceus Moench (Leguminosae), has been shown to exert potent cardioprotective and anti-inflammatory effects. It is still unclear whether AST IV has a latent effect on the proinflammatory ability of HMGB1 with subsequent activation of Tregs in vivo.
  
  
  OBJECTIVE
  This research explores the antagonism of different doses of AST IV on the immunologic function of Tregs mediated by HMGB1.
  
  
  METHODS
  Mouse models (BALB/c) were constructed by which normal saline or AST IV was administered i.p. at 2, 4 and 6 days after the administration i.p. of 20 μg recombinate HMGB1. Spleen was used to procure Treg and CD4+CD25-T-cells which were co-cultured with Treg. Cell phenotypes of Tregs(Foxp3) were examined, and the cytokine levels in supernatants and the proliferation of T-cells were assayed. Gene expression was measured by RT-PCR.
  
  
  RESULTS
  (1) The expression levels of Foxp3 in Treg on post-stimulus days (PSD) 1-7 were significantly decreased in the HMGB1 group in comparison to those in the control group mice (p < 0.01). The Foxp3 expression was markedly increased in a dose-dependent manner in the AST group as compared with those in the HMGB1 group (p < 0.0 1-0.05). The same results were found in the contents of cytokines (IL-10 and TGF-β) released into supernatants by Treg. (2) When CD4+CD25-T-cells were co-cultured with Treg stimulated by HMGB1, the cell proliferation and the levels of cytokines (IL-2 and IFN-γ) in supernatant were markedly increased as compared with those in the HMGB1 group. The level of IL-4 was markedly decreased as compared with that in the HMGB1 group. The same results were found when CD4+CD25-T-cells were co-cultured with Treg in the NS group. Compared with those in the NS group, the contrary results were shown in a dose-dependent manner in the AST group.
  
  
  CONCLUSIONS
  These results showed that AST IV has a therapeutic effect on inflammation promoted by HMGB1, and it should be studied as a new drug for the treatment of sepsis.
authors: a Department of Obstetrics and Gynecology , Beijing Chao-Yang Hospital, Capital Medical University , Beijing , China.
authors: Jinfeng
authors: J
authors: Li
authors: b Department of Surgical Intensive Care Unit , Beijing Chao-Yang Hospital, Capital Medical University , Beijing , China.
authors: Lifeng
authors: L
authors: Huang
authors: a Department of Obstetrics and Gynecology , Beijing Chao-Yang Hospital, Capital Medical University , Beijing , China.
authors: Shuzhen
authors: S
authors: Wang
authors: c Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital , Beijing , China.
authors: Yongming
authors: Y
authors: Yao
authors: a Department of Obstetrics and Gynecology , Beijing Chao-Yang Hospital, Capital Medical University , Beijing , China.
authors: Zhenyu
authors: Z
authors: Zhang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012503:Saponins / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D004365:Drugs, Chinese Herbal; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D018836:Inflammation Mediators; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A
keywords: High mobility group box 1 protein; immunity; inflammation