Reynoutrin inhibits Th1 and Th17 differentiation to attenuate DSS-induced colitis by targeting Notch3

We employed dextran sulfate sodium (DSS)-induced colitis as a mouse model to dissect the impact of reynoutrin on disease progression. Weight monitoring, pathological score, immunohistochemistry staining, and flow cytometry analysis were performed. To investigate the underlying mechanisms, we extensively examined the differentiation of effector T (Teff) cells and their related molecular targets upon reynoutrin treatment.

Results: We found that reynoutrin treatment improved DSS-induced colitis, manifested by the alleviated weight loss, colon shortening, and structure disruption. In addition, reynoutrin‑treated mice showed significantly decreased Th1 and Th17 cells in the mesenteric lymph nodes (MLNs) and colonic tissues. Mechanistic studies revealed that reynoutrin restrained Teff cell differentiation and production of proinfammatory cytokines through inhibiting Notch3.

Importantly, our data showed that reynoutrin was safe and well-tolerated in mice. Conclusions: Reynoutrin could protect mice against DSS-induced colitis by diminishing Th1 and Th17 differentiation and may be therapeutically beneficial for IBD patients.