EGCG ameliorates ulcerative colitis in mice via inhibition of the Notch signaling pathway

Ulcerative colitis (UC) is a type of inflammatory bowel disease. (−)-Epigallocatechin-3-gallate (EGCG) has been shown to alleviate UC; however, the underlying mechanisms by which EGCG improves UC remain unclear. Previous studies have indicated that the Notch signaling pathway plays a role in the pathogenesis of UC, and our preliminary research has identified Notch as an inflammatory target of EGCG. Therefore, this study aims to investigate the potential mechanism by which EGCG may alleviate UC through modulation of the Notch pathway. In this study, EGCG treatment reduced the secretion of inflammatory cytokines and the expression of inflammatory proteins in lipopolysaccharide (LPS)-stimulated human epithelial colorectal adenocarcinoma (Caco-2) cells. Furthermore, EGCG downregulated the protein expression levels of Notch1, Cleaved-Notch1, and Hes-1 in LPS-induced Caco-2 cells. These results demonstrate that EGCG alleviates inflammatory injury in intestinal epithelial cells by inhibiting the Notch signaling pathway. Oral administration of EGCG decreased the secretion of pro-inflammatory cytokines in the colon of dextran sulfate sodium (DSS)-induced mice and attenuated macrophage infiltration into the colon. We also found that EGCG suppressed the polarization of macrophages toward the M1 phenotype in the colon. More importantly, EGCG significantly reduced the protein expression levels of Notch1, Cleaved-Notch1, and Hes-1 in the colon. These findings suggest that EGCG alleviates M1-type macrophage polarization by inhibiting the Notch pathway, thereby improving UC. This provides a new therapeutic strategy for the treatment of UC. • EGCG attenuates inflammation induced by LPS through the inhibition of Notch signaling in Caco-2 cells. • EGCG inhibits the levels of inflammatory cytokines and the polarization of M1 macrophages in the colon tissues of mice with colitis induced by DSS. • EGCG suppresses the expression levels of Notch in the colon tissues of mice with DSS-induced colitis. • EGCG alleviates DSS-induced colitis by inhibiting the Notch-M1 axis. This provides a potential strategy for the treatment of inflammatory bowel disease.