Schisandrin B inhibits Th1/Th17 differentiation and promotes regulatory T cell expansion in mouse lymphocytes

Int Immunopharmacol. 2016 Jun:35:257-264. doi: 10.1016/j.intimp.2016.03.037. Epub 2016 Apr 16.

Abstract

Schisandrin B (Sch-B), the most abundant active ingredient of the fruit of Schisandra chinensis, has been proposed to have antioxidant, anti-tumor and anti-inflammatory effects. The present study was undertaken to investigate the effect of Sch-B on differentiation of T helper cells (Th). Using mouse splenic lymphocytes stimulated with concanavalin A (Con A) in vitro and ex vivo as inflammation models, we found that Sch-B significantly inhibited secretion of Th1 and Th17 related cytokines, such as IFN-γ and IL-17. In addition, we found that Sch-B suppressed the differentiation of naive CD4+ T cells into Th1 and Th17 cells, while promoted their differentiation into the regulatory T cells (Treg) in vitro. We further found that Sch-B suppressed transcription of Th1-related T-box transcription factor, T-bet, and Th17-related transcription factor, retinoid related orphan receptor gamma t (RORγt), while enhanced transcription of Treg-related transcription factor forkhead box protein 3 (Foxp3) in naive CD4+ T cells under Th cell polarization conditions. Furthermore, the effect of Sch-B on the T cell differentiation was abrogated by heme oxygenase-1 (HO-1) inhibitor zinc protoporphyrin. Taken together, we conclude that Sch-B can modulate differentiation of naïve CD4+ T cells into specific lineages of effector cells, which may have potential benefits for treatment of autoimmune diseases.

Keywords: Cytokines; Immunomodulatory; Schisandrin B; T helper cells.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclooctanes / pharmacology
  • Cytokines / metabolism
  • Forkhead Transcription Factors / metabolism
  • Heme Oxygenase-1 / metabolism
  • Immunosuppression Therapy
  • Lignans / pharmacology*
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Polycyclic Compounds / pharmacology*
  • Schisandra / immunology*
  • T-Box Domain Proteins / metabolism
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • T-bet Transcription Factor
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology

Substances

  • Cyclooctanes
  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Lignans
  • Membrane Proteins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Polycyclic Compounds
  • T-Box Domain Proteins
  • T-bet Transcription Factor
  • schizandrin B
  • Heme Oxygenase-1
  • Hmox1 protein, mouse