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

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 in-testinal 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 symp-toms 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-alpha, IL-1 beta, 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.

Automated summary

AA can prevent colitis by enhancing intestinal barrier function through suppressing the Notch signaling pathway. Oral administration of AA can alleviate colitis symptoms, inhibit inflammation, promote normal cell proliferation, and increase the expression of tight junction proteins and mucus secretion in the intestinal wall.