Periplaneta americana extract ameliorates dextran sulfate sodium-induced ulcerative colitis via immunoregulatory and PI3K/AKT/NF-κB signaling pathways

Inflammopharmacology. 2022 Jun;30(3):907-918. doi: 10.1007/s10787-022-00955-7. Epub 2022 Mar 18.

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) with a low cure rate. Periplaneta americana is a traditional American Cockroach and reportedly has potential therapeutic roles for UC treatment; however, its mechanisms remain unclear. To address this, we investigated the therapeutic effects and underlying molecular mechanisms of Ento-A, a Periplaneta americana extract, in a dextran sulfate sodium (DSS)-induced chronic and recurrent UC mouse model. Ento-A treatment decreased pro-inflammatory cytokine secretion, disease activity index (DAI), colon mucosa damage index (CMDI), histopathological scores (HS), and increased colon length. Additionally, Ento-A effectively increased interleukin-4 (IL-4), and forkhead transcription factor protein 3 (Foxp3) expression levels, while it abated interferon-γ (IFN-γ) and IL-17 levels in spleen lymphocytes. Conversely, in mesenteric lymph nodes, IL-4 and Foxp3 expression were decreased, while IFN-γ and IL-17 expression was increased. Furthermore, Ento-A blocked p-PI3K, p-AKT,*and p-NF-κB activation. In conclusion, Ento-A improved UC symptoms and exerted therapeutic effects by regulating immune responses and inhibiting PI3K/AKT/NF-κB signaling.

Keywords: Dextran sulfate sodium; Immune regulation; PI3K/AKT/NF-κB signaling pathway; Periplaneta americana; Ulcerative colitis.

MeSH terms

  • Animals
  • Colitis* / drug therapy
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / pathology
  • Colon
  • Dextran Sulfate / pharmacology
  • Disease Models, Animal
  • Forkhead Transcription Factors / metabolism
  • Immunity
  • Interleukin-17 / metabolism
  • Interleukin-4 / metabolism
  • Mice
  • NF-kappa B / metabolism
  • Periplaneta* / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction

Substances

  • Forkhead Transcription Factors
  • Interleukin-17
  • NF-kappa B
  • Plant Extracts
  • Interleukin-4
  • Dextran Sulfate
  • Proto-Oncogene Proteins c-akt