The effect of Astragaloside IV on immune function of regulatory T cell mediated by high mobility group box 1 protein in vitro

Fitoterapia. 2012 Dec;83(8):1514-22. doi: 10.1016/j.fitote.2012.08.019. Epub 2012 Sep 5.


High mobility group box 1 protein (HMGB1), a potent pro-inflammatory cytokine, contributes to the pathogenesis of diverse inflammatory and infectious disorders. Some studies have illustrated the potential effect of HMGB1 on regulatory T cells (Tregs). Astragaloside IV (AST IV) isolated from a Chinese herb, Astragalus mongholicus, is known to have a variety of immunomodulatory activities. However, it is not yet clear whether AST IV possesses potential regulatory effect on the pro-inflammatory ability of HMGB1 with subsequent activation of Tregs. This study was carried out to investigate the antagonistic effects of different doses of AST IV on the immune function of Tregs mediated by HMGB1 in vitro. Tregs isolated from the spleens of mice were co-cultured with HMGB1 and/or AST IV. Cell phenotypes of Tregs were analyzed, and the contents of various cytokines in the cell supernatants as a result of co-culture and the proliferation of CD4(+)CD25(-) T cells were determined. Results showed that HMGB1 stimulation resulted in significantly down-regulation of expressions of Tregs cell phenotypes. However, AST IV can rival the suppressing effect of HMGB1 on immune function of Tregs with a dose-dependent in vitro. These results indicate that AST IV has the potential therapeutic action on inflammation augmented by HMGB1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / genetics
  • CD4 Antigens / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation / physiology
  • HMGB1 Protein / genetics
  • HMGB1 Protein / metabolism*
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Male
  • Mice
  • Molecular Structure
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Saponins / chemistry
  • Saponins / pharmacology*
  • Spleen / cytology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*


  • CD4 Antigens
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • HMGB1 Protein
  • Interleukin-2 Receptor alpha Subunit
  • RNA, Messenger
  • Saponins
  • Transforming Growth Factor beta
  • Triterpenes
  • Interleukin-10
  • astragaloside A