Total Flavonoids of Astragalus Inhibit Activated CD4[Formula: see text] T Cells and Regulate Differentiation of Th17/Th1/Treg Cells in Experimental Autoimmune Encephalomyelitis Mice by JAK/STAT and NF[Formula: see text]B Signaling Pathways

Am J Chin Med. 2023;51(5):1233-1248. doi: 10.1142/S0192415X23500568. Epub 2023 Jun 30.

Abstract

Multiple sclerosis (MS) is a neuroinflammatory disease characterized by CD4[Formula: see text] T cell-mediated immune cell infiltration and demyelination in the central nervous system (CNS). The subtypes of CD4[Formula: see text] T cells are T helper cells 1 (Th1), Th2, Th17, and regulatory T cells (Treg), while three other types of cells besides Th2 play a key role in MS and its classic animal model, experimental autoimmune encephalomyelitis (EAE). Tregs are responsible for immunosuppression, while pathogenic Th1 and Th17 cells cause autoimmune-associated demyelination. Therefore, suppressing Th1 and Th17 cell differentiation and increasing the percentage of Treg cells may contribute to the treatment of EAE/MS. Astragali Radix (AR) is a representative medicine with immunoregulatory, anti-inflammatory, antitumor, and neuroprotective effects.The active ingredients in AR include astragalus flavones, polysaccharides, and saponins. In this study, it was found that the total flavonoids of Astragus (TFA) could effectively treat EAE in mice by ameliorating EAE motor disorders, reducing inflammatory damage and demyelination, inhibiting the proportion of Th17 and Th1 cells, and promoting Tregs differentiation by regulating the JAK/STAT and NF[Formula: see text]B signaling pathways. This novel finding may increase the possibility of using AR or TFA as a drug with immunomodulatory effects for the treatment of autoimmune diseases.

Keywords: Astragalus; Differentiation; Th1 Cells; Th17 Cells; Total Flavonoids; Treg Cells.

MeSH terms

  • Animals
  • Cell Differentiation
  • Encephalomyelitis, Autoimmune, Experimental* / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental* / metabolism
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction
  • T-Lymphocytes, Regulatory
  • Th1 Cells
  • Th17 Cells

Substances

  • Flavonoids