A Novel Selenium-Based Nanozyme (GSH-Se) Ameliorates Colitis in Mice by Modulating the Nrf2/Keap1 and GPx4 Pathways.

Combination of selenium (Se) and glutathione peroxidase (GPx) can reduce the dose of Se used while concurrently exploiting their antioxidative performance, which can be used as a potential treatment for ulcerative colitis. Nanozymes possess higher stability, are more economical, and have more multifunctionalities than natural enzymes and thus could be an ideal approach for their combination. Therefore, this study synthesised a nanozyme using glutathione (GSH) and Se-GSH-Se-and evaluated its alleviating effects on colitis in mice induced by dextran sulphate sodium salt (DSS). Three doses of GSH-Se, 6 mM, 12 mM, and 18 mM were supplemented in DSS-induced colitis in mice. Findings showed that GSH-Se supplementation ameliorated colitis by improving the colonic mucosal integrity, reducing inflammatory responses and oxidative stress, and alleviating gut microbiota imbalance in mice with DSS-induced colitis. Moreover, an in vitro experiment was performed to unravel the molecular mechanism by which GSH-Se ameliorated colitis in mice, based on lipopolysaccharide-induced inflammation in mouse colon epithelial cells. The results suggested that the alleviating effects of GSH-Se on mouse colitis was likely mediated by the activation of the Nrf2/Keap1 (nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1) and GPx4 signalling pathways.