Colitis can be Improved by (−)-Epigallocatechin Gallate through Targeting Notch in DSS-induced UC mice

Abstract Background: Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease. Previous research shows that Notch plays a role in the pathogenesis of UC and (−)-Epigallocatechin Gallate(EGCG) could attenuate colitis. However, the mechanism of EGCG to improve colitis remains unclear. Methods:The human epithelial colorectal adenocarcinoma Caco-2 cells were intervened with EGCG (10ug/ml or 30ug/ml) with or without Lipopolysaccharide. A mouse model of UC was induced by 3% dextran sulfate sodium and EGCG treatment was administered to mice at a dose of 10 and 20 mg/kg. The stool consistency, rectal bleeding and weight were recorded daily. The disease activity index (DAI) of mice was calculated, and the pathological injury scores were assessed through hematoxylin and eosin staining. Immunohistochemical analyses were performed for iNOS, F4/80, Notch1 and hes1. Inflammatory cytokines were detected using ELISA kits .Western blot assays were performed for TNF-α, IL-1β, , Notch1, Cleaved-Notch1, Notch2,, Hes-1, COX2, iNOS from colon tissues and Caco-2 cells. Results: In this study, we found that the cytokine secretion and inflammation protein expression were reduced with EGCG treatment in LPS induced Caco-2 cells. And the levels of Notch1, Cleaved-Notch1, and Hes-1 expression were decreased by EGCG administration in the cell. Moreover, we found the pro-inflammation cytokine secretion and the macrophages accumulation were reduced by oral EGCG in DSS-induced mice colon which indicates EGCG ameliorates colitis in vivo. And we also found the phenotype of macrophages could alter to M1 was inhibited by oral EGCG in vivo. In addition, we demonstrate that EGCG could attenuate the levels of Notch1, Cleaved-Notch1, and Hes-1 expression in the colon. Conclusion: This study demonstrates that colitis can be improved by EGCG through targeting Notch in DSS-induced UC mice. Key words: EGCG; Notch; colitis; inflammation