Polydatin alleviates DSS- and TNBS-induced colitis by suppressing Th17 cell differentiation via directly inhibiting STAT3

Phytother Res. 2022 Sep;36(9):3662-3671. doi: 10.1002/ptr.7533. Epub 2022 Jun 29.

Abstract

Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disease, often presenting with abdominal pain, diarrhea, bloody stool, anorexia, and body loss. It is difficult to cure completely and a promising treatment is urgently needed. Natural compounds can offer promising chemical agents for treatment of diseases. Polydatin is a natural ingredient extracted from the dried rhizome of Polygonum cuspidatum, which has anti-inflammatory, anti-tumor, and dementia protection activities. The purpose of this study was to evaluate the therapeutic effect of polydatin on IBD and explore its possible mechanism. We found that polydatin could effectively suppress the differentiation of Th17 cells in vitro, but had no effect on the differentiation of Treg cells. Polydatin significantly alleviated colitis induced by dextran sulfate sodium (DSS) and 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) in mice, and dramatically decreased the proportion of Th17 cells in spleen and mesenteric lymph nodes. Mechanism investigations revealed that polydatin specifically inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation by directly binding to STAT3, leading to Th17 cell reduction and thereby alleviating colitis. These findings provide novel insights into the anti-colitis effect of polydatin, which may be a promising drug candidate for the treatment of IBD.

Keywords: Polydatin; STAT3; Th17; differentiation; inflammatory bowel disease.

MeSH terms

  • Animals
  • Cell Differentiation
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Colon
  • Dextran Sulfate
  • Disease Models, Animal
  • Glucosides
  • Inflammatory Bowel Diseases* / pathology
  • Mice
  • Mice, Inbred C57BL
  • STAT3 Transcription Factor / metabolism
  • Stilbenes
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells
  • Trinitrobenzenesulfonic Acid / metabolism

Substances

  • Glucosides
  • STAT3 Transcription Factor
  • Stilbenes
  • Trinitrobenzenesulfonic Acid
  • Dextran Sulfate
  • polydatin