Sinomenine hydrochloride improves DSS-induced colitis in mice through inhibition of the Notch signaling pathway

BMC Gastroenterol. 2024 Dec 18;24(1):451. doi: 10.1186/s12876-024-03546-8.

Abstract

Objective: To study the therapeutic effect of sinomenine hydrochloride (SH) on dextran sodium sulfate (DSS)-induced colitis in mice as an animal model and the changes of Notch signaling pathway in colon tissue of mice after treatment.

Methods: Twenty-four mice were randomly divided into control group, model group, SH low-dose group (20 mg/kg) and SH high-dose group (60 mg/kg), with 6 mice in each group. Disease activity index (DAI), colonic mucosal injury index and colonic histopathological score were calculated. The expression levels of related genes, proteins in Notch signaling pathway and inflammatory factors were quantified.

Results: SH can significantly reduce the symptoms of colitis mice, and can significantly reduce the DAI score (Model: 3.44 ± 0.27; SH-20: 2.50 ± 0.18; SH-60: 1.89 ± 0.17; P < 0.001) and histopathological injury degree (Model: 7.67 ± 0.52; SH-20: 5.17 ± 0.75, P < 0.01; SH-60: 3.33 ± 0.52, P < 0.001). SH can down-regulate the expression levels of Notch1, NICD1, Jagged1 and Hes1 proteins in colon tissue of colitis mice (Model: 1.92 ± 0.16, 1.83 ± 0.21, 2.23 ± 0.22, 1.91 ± 0.17; SH-20: 1.56 ± 0.12, 1.39 ± 0.13, 1.58 ± 0.12, 1.38 ± 0.11; SH-60: 1.24 ± 0.09, 1.23 ± 0.10, 1.23 ± 0.11, 1.22 ± 0.09; P < 0.01), and reduce the contents of serum pro-inflammatory cytokines TNF-α, IL-1β and IL-6 (Model: 718.53 ± 81.81, 51.62 ± 2.80, 444.07 ± 67.77; SH-20: 544.72 ± 90.03, 34.10 ± 2.90, 345.43 ± 43.40; SH-60: 434.11 ± 71.75, 29.44 ± 3.70, 236.11 ± 29.35; P < 0.001).

Conclusion: The therapeutic effect of SH on DSS-induced colitis in mice may be related to inhibiting the overactivation of Notch signaling pathway.

Keywords: Disease activity index; Notch signaling pathway; Sinomenine hydrochloride; Ulcerative colitis.

MeSH terms

  • Animals
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Colitis* / metabolism
  • Colitis* / pathology
  • Colon* / drug effects
  • Colon* / metabolism
  • Colon* / pathology
  • Dextran Sulfate*
  • Disease Models, Animal*
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Jagged-1 Protein / metabolism
  • Male
  • Mice
  • Morphinans* / pharmacology
  • Morphinans* / therapeutic use
  • Receptor, Notch1 / metabolism
  • Receptors, Notch / metabolism
  • Signal Transduction* / drug effects
  • Transcription Factor HES-1 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • sinomenine
  • Morphinans
  • Dextran Sulfate
  • Tumor Necrosis Factor-alpha
  • Receptors, Notch
  • Jagged-1 Protein
  • Interleukin-6
  • Receptor, Notch1
  • Interleukin-1beta
  • Transcription Factor HES-1