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.