Aloin A prevents ulcerative colitis in mice by enhancing the intestinal barrier function via suppressing the Notch signaling pathway

Phytomedicine. 2022 Nov:106:154403. doi: 10.1016/j.phymed.2022.154403. Epub 2022 Aug 19.

Abstract

Background: Previous studies reported that Aloe vera ameliorated DSS-induced colitis and promoted mucus secretion. However, the effect of Aloin A (AA), a major compound of Aloe vera, on colitis and its exact mechanism remains uncovered.

Methods: C57BL/6 mice were successively subjected to 3% DSS solution for 5 days and distilled water for 2 days. Concurrently, AA (25, 50 mg/kg) and 5-aminosalicylic (500 mg/kg) were administrated intragastrically from day 1 to day 7. Colitis was evaluated by disease active index (DAI), colon length, inflammation response, and intestinal barrier function. In vitro LS174T cells challenged with 50 ng/ml of lipopolysaccharides (LPS) were used to validate the modulatory action of AA on the Notch signaling pathway.

Results: Our results showed that oral administration with AA prominently prevented DSS-induced colitis symptoms in terms of decreased DAI, prevention of colon shortening, and reduced pathological damage. AA mitigated the inflammatory response evidenced by the decreased proinflammatory cytokines (TNF-α, IL-1β, IL-6) and increased anti-inflammatory cytokine (IL-10). Besides, AA inhibited apoptosis and facilitated proliferation in colons. Moreover, AA treatment up-regulated the expression of tight junction (TJ) proteins (ZO-1, Occludin) and promoted the secretion of MUC2 to decrease colon permeability. Mechanistically, AA inhibited the Notch pathway to promote the secretion of MUC2, which was consistent with LPS-challenged LS174 cells.

Conclusion: These results suggested that AA could prevent colitis by enhancing the intestinal barrier function via suppressing the Notch signaling pathway. Thus, AA might be a prospective remedy for ulcerative colitis.

Keywords: Aloin A; Intestinal barrier; Notch; Ulcerative colitis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Colitis* / prevention & control
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / prevention & control
  • Colon / pathology
  • Cytokines / metabolism
  • Dextran Sulfate / adverse effects
  • Disease Models, Animal
  • Emodin / analogs & derivatives
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • Intestinal Mucosa / metabolism
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Occludin / metabolism
  • Prospective Studies
  • Signal Transduction
  • Tight Junction Proteins / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Water

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Interleukin-6
  • Lipopolysaccharides
  • Occludin
  • Tight Junction Proteins
  • Tumor Necrosis Factor-alpha
  • Water
  • Interleukin-10
  • Dextran Sulfate
  • Emodin
  • alloin