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.