Gegen Qinlian decoction relieved DSS-induced ulcerative colitis in mice by modulating Th17/Treg cell homeostasis via suppressing IL-6/JAK2/STAT3 signaling

Phytomedicine. 2021 Apr:84:153519. doi: 10.1016/j.phymed.2021.153519. Epub 2021 Feb 18.

Abstract

Background: Gegen Qinlian decoction (GQ) is a traditional Chinese herbal prescription that has been widely used for the treatment of bacterial dysentery and enteric typhoid fever. Recently, GQ has been clinically reported to be a potential candidate for the treatment of ulcerative colitis (UC). However, the immunoregulatory function of GQ in the treatment of UC has not been fully elucidated.

Purpose: This study focused on the role of immune imbalance in the pathogenesis of UC and the immunomodulatory effect of GQ in the treatment of UC.

Methods: The UC model was established by treating female mice with 3.0% dextran sulfate sodium (DSS) for 7 days, and GQ was orally administered at dosages of 1.5 and 7.5 g/kg/day. Inflammatory factors were detected by ELISA and qRT-PCR. Treg and Th17 cell dysregulation was analyzed by qRT-PCR, immunohistochemistry and flow cytometry. Proteins related to IL-6/JAK2/STAT3 signaling were detected by western blotting.

Results: GQ significantly alleviated the symptoms of UC mice and suppressed the activity of myeloperoxidase (MPO). Furthermore, the production of proinflammatory factors, such as IL-1β, TNF-α and IL-6, was dramatically reduced after GQ administration. Furthermore, GQ improved the infiltration of Treg and Th17 cells into the colons and decreased the expression of inflammatory factors, such as TGF-β1 and IL-17. The frequencies of Treg and Th17 cells in the Peyer's patches and spleen were reduced by GQ administration; however, GQ had no significant regulatory effect on normal mice. The western blotting results showed that GQ markedly suppressed the phosphorylation of JAK2 and STAT3 and decreased the transcription function of phosphorylated STAT3.

Conclusions: Taken together, these results indicated that GQ alleviated DSS-induced UC by suppressing IL-6/JAK2/STAT3 signaling to restore Treg and Th17 cell homeostasis in colonic tissue.

Keywords: Gegen Qinlian decoction; IL-6/JAK2/STAT3 signaling; Immunoregulatory; Treg and Th17 cells; Ulcerative colitis.

MeSH terms

  • Animals
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / metabolism
  • Colon / drug effects
  • Colon / immunology
  • Colon / metabolism
  • Colon / pathology
  • Dextran Sulfate / toxicity
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Homeostasis / drug effects
  • Immunologic Factors / pharmacology
  • Interleukin-17 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Janus Kinase 2 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Peroxidase / metabolism
  • Peyer's Patches / drug effects
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology

Substances

  • Drugs, Chinese Herbal
  • Il17a protein, mouse
  • Immunologic Factors
  • Interleukin-17
  • Interleukin-6
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • gegenqinlian
  • interleukin-6, mouse
  • Dextran Sulfate
  • Peroxidase
  • Jak2 protein, mouse
  • Janus Kinase 2