Acteoside alleviates dextran sulphate sodium-induced ulcerative colitis via regulation of the HO-1/HMGB1 signaling pathway

Ulcerative colitis (UC) is a significant burden on human health, and the elucidation of the mechanism by which it develops has potential for the prevention and treatment of UC. It has been reported that acteoside (ACT) exhibits strong anti-inflammatory activity. In the present study, it was hypothesized that ACT may exert a protective effect against UC. The effects of ACT on inflammation, oxidative stress and apoptosis were evaluated using dextran sulphate sodium (DSS)-treated mice and DSS-treated human colorectal adenocarcinoma Caco-2 cells, which have an epithelial morphology. The results demonstrated that the ACT-treated mice with DSS-induced UC exhibited significantly reduced colon inflammation, as demonstrated by a reversal in body weight loss, colon shortening, disease activity index score, inflammation, oxidative stress and colonic barrier dysfunction. Further in vivo experiments demonstrated that ACT inhibited DSS-induced apoptosis in colon tissues, as demonstrated by the results of the TUNEL assay and the altered protein expression levels of Bax, cleaved caspase-3 and Bcl-2. Furthermore, DSS significantly stimulated the protein expression levels of high mobility group box 1 protein (HMGB1), which serves a central role in the initiation and progression of UC, an effect which was markedly inhibited by ACT. Finally, DSS significantly decreased the protein expression levels of heme oxygenase-1 (HO-1) in colon tissues and the effect of ACT on GSH, apoptotic proteins and HMGB1 was markedly attenuated in the presence of the HO-1 inhibitor tin protoporphyrin. In conclusion, ACT ameliorated colon inflammation through HMGB1 inhibition in a HO-1-dependent manner.