Shikimic Acid Regulates the NF-κB/MAPK Signaling Pathway and Gut Microbiota to Ameliorate DSS-Induced Ulcerative Colitis

J Agric Food Chem. 2023 Jun 14;71(23):8906-8914. doi: 10.1021/acs.jafc.3c00283. Epub 2023 May 31.

Abstract

Shikimic acid (SA) is a compound extracted from the plant anise and has anti-inflammatory effects. However, any impact on intestinal inflammation or mechanisms involved has not been investigated. The present study used a dextran sulfate sodium (DSS)-induced mouse colitis model to investigate the effects of SA on intestinal inflammation. Intragastric administration of SA slowed DSS-induced weight loss, reduced disease activity index (DAI) score, enhanced the intestinal barrier, reduced the destruction of the colonic structure, inhibited the phosphorylation of key proteins in MAPK and NF-κB signaling pathways, inhibited the expression of inflammatory factors TNF-α, IL-1β, and MPO (P < 0.05), decreased IFN-γ expression (P < 0.05), and increased immunoglobulin IgG content (P < 0.05). After 50 mg/kg SA treatment, the content of Bacteroidetes increased and Proteobacteria decreased in the cecal feces of mice with colitis (P < 0.05) and the richness of gut species increased. In conclusion, SA could improve intestinal inflammation and enhance intestinal immunity, indicating its suitability as a therapeutic candidate.

Keywords: intestinal barrier function; intestinal flora; shikimic acid; tight junction protein; ulcerative colitis.

MeSH terms

  • Animals
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Colitis* / genetics
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / genetics
  • Colon / metabolism
  • Dextran Sulfate / metabolism
  • Disease Models, Animal
  • Gastrointestinal Microbiome*
  • Inflammation / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Shikimic Acid / metabolism
  • Signal Transduction

Substances

  • NF-kappa B
  • Shikimic Acid
  • Dextran Sulfate