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