A hydroxyethyl derivative of chrysin exhibits anti-inflammatory activity in dendritic cells and protective effects against dextran sodium salt-induced colitis in mice

Int Immunopharmacol. 2019 Dec:77:105958. doi: 10.1016/j.intimp.2019.105958. Epub 2019 Oct 19.

Abstract

Inflammatory bowel disease (IBD) is a chronic disease that occurs in the intestinal tract. Phyto-ingredients have been evaluated for their ability to protect against IBD because of their anti-inflammatory activities. In our previous study, we identified a novel derivative of chrysin (HE-chrysin) using irradiation technology, which exhibited stronger anti-cancer activity in human colorectal cancer cells than the original chrysin. Here, to determine whether HE-chrysin is a new therapeutic candidate for IBD, we investigated the anti-inflammatory effects of HE-chrysin on bone marrow-derived dendritic cells (BMDCs) and dextran sodium salt (DSS)-induced colitis in mice. HE-chrysin more effectively inhibited BMDC maturation compared to chrysin, as demonstrated by the decreased levels of pro-inflammatory cytokines, surface molecules, antigen-presenting ability, and T cell proliferation/activation in lipopolysaccharide-stimulated BMDCs. These anti-inflammatory effects of HE-chrysin were regulated by mitogen-activated protein kinases and nuclear factor-κB. Furthermore, oral administration of HE-chrysin attenuated DSS-induced colitis symptoms and clinical signs in the mouse model. The protective effects of HE-chrysin treatment against colitis were mediated by decreasing Th1- and Th17-type cytokine levels. These results indicate that HE-chrysin is attractive candidate for IBD therapy.

Keywords: Anti-inflammation; Chrysin derivative; DSS-induced colitis; Dendritic cells; Flavonoids; Inflammatory bowel disease.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Cytokines / metabolism
  • Dendritic Cells / drug effects*
  • Dendritic Cells / metabolism
  • Dextran Sulfate / pharmacology
  • Disease Models, Animal
  • Female
  • Flavonoids / pharmacology*
  • Inflammation Mediators / metabolism
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / metabolism
  • Lipopolysaccharides / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Protective Agents / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Flavonoids
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Protective Agents
  • chrysin
  • Dextran Sulfate