The protective effect and mechanism of pedunculoside on DSS (dextran sulfate sodium) induced ulcerative colitis in mice

Int Immunopharmacol. 2020 Nov:88:107017. doi: 10.1016/j.intimp.2020.107017. Epub 2020 Sep 22.

Abstract

Pedunculoside (PE) is derived from the bark of iron holly, a member of the holly family. Previous studies have shown that PE has anti-inflammatory, antitumor, antiviral, cholesterol-lowering and blood-pressure-lowering effects. In this study, we aimed to investigate the effects of PE on ulcerative colitis and to explore its potential mechanisms. We treated a mouse model of ulcerative colitis induced by DSS (dextran sulfate sodium) with PE. The results showed that PE had an obvious effect on DSS-induced ulcerative colitis. PE significantly improved the colon length and clinical score in mice, and significantly inhibited the production of inflammatory cytokines. In the LPS-induced inflammatory response of RAW264.7 macrophages, we also found that PE significantly inhibited the phosphorylation of AKT, ERK1/2, JNK1/2, P65, and P38 to reduce the production of IL-1β, IL-6, TNF-α, COX-2, and iNOS. Furthermore, PE suppressed the LPS-induced transcriptional activities of nuclear factor P65 as well as the phosphorylation of P65. In addition, we also studied the effect of PE on LPS induced AKT/NF-κB and MAPK signaling pathways with primary peritoneal macrophages. In summary, PE has a beneficial effect on ulcerative colitis, and may be a potential natural product in the treatment of ulcerative colitis.

Keywords: AKT/NF-κB; MAPK; Pedunculoside; RAW264.7 macrophages; Ulcerative colitis.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Colitis, Ulcerative / chemically induced*
  • Colitis, Ulcerative / prevention & control*
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Dextran Sulfate / toxicity*
  • Gene Expression Regulation / drug effects
  • Glucose / analogs & derivatives*
  • Glucose / chemistry
  • Glucose / pharmacology
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Lipopolysaccharides / toxicity
  • Macrophages / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • RAW 264.7 Cells
  • Random Allocation
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*

Substances

  • Cytokines
  • Lipopolysaccharides
  • Triterpenes
  • pedunculoside
  • Dextran Sulfate
  • Glucose