Introduction
Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel
disease (IBD), which is characterized by complicated and relapsing
inflammation caused enormous multidimensional burdens on patients and
health care systems1. Over 1 million residents in the
USA and 2.5 million in Europe are estimated to have IBD and it also has
emerged in newly industrialized countries in Asia, South America, and
the Middle East and has evolved into a global disease with rising
prevalence in every continent2. In China, the
age-standardized rate of prevalence and incidence of IBD was increased
between 1990 and 20171. It can impede career
aspirations, instill social stigma and impair quality of life in
patients1,3. Some drug-like anti-inflammatory,
immunosuppressive, 5-aminosalicylic acid or corticosteroids, have been
used in clinical UC patients. But these clinical medicines are no cure
for relapsing and there are certain side effects3,4.
Hence, it is necessary to find some new and safer treatment drugs, such
as natural products.
The pathogenesis of UC includes environmental factors, genetic
predisposition, dysregulated immune responses, mucous barrier and so
on5. However, the pathogenesis of UC is still unclear.
The Notch signaling pathway is a major regulator of cell-fate
determination during development and cellular
differentiation6. Some studies have been reported that
the Notch signaling pathway plays a role in the pathogenesis of
UC7,8. And Notch could ensure integrity and
homeostasis of the intestinal epithelium7. It also
plays a role in regulating inflammatory respond6.
Thus, Notch maybe as a potential target to treatment UC.
The (−)-Epigallocatechin-3-gallate (EGCG) is a kind of polyphenol that
is abundant in tea9. Previous study has been reported
that EGCG could attenuate colitis which induced by dextran sulfate
sodium (DSS)10. However, the mechanism of EGCG to
improve colitis remains unclear. In our previous studies, we have
demonstration that Notch is a receptor of EGCG11,12.
Thus, we hypothesized that EGCG may attenuate colitis in UC mice by
targeting Notch1 to inhibit inflammation.
To prove this hypothesis, the human epithelial colorectal adenocarcinoma
Caco-2 cell line13 and DSS-induced UC model of C57
mice4 were used to study the effects of EGCG on Notch1
to attenuate colitis. The results showed that the activation of Notch1
was attenuated by treatment with EGCG in vitro and in vivo. Furthermore,
the inflammation response and clinical symptoms of colitis in UC mice
can be also improved by EGCG. These findings suggest that EGCG can
attenuate colitis by targeting Notch1. Therefore, the identification
effect of EGCG on Notch1 provides a new idea for the treatment of UC and
EGCG as a potential drug for the treatment of IBD.