Cinnamtannin D1 ameliorates DSS-induced colitis by preventing Th17/Treg imbalance through activation of the AMPK/mTOR pathway.

Background: Inflammatory bowel disease (IBD) is a chronic idiopathic gastrointestinal disease, including ulcerative colitis (UC) and Crohn's disease (CD), which is typically characterized by chronicity and relapse. Cinnamtannin D1 (CTD1), extracted from , has been found to exert good immunosuppressive activity. However, the role of CTD1 in IBD is unclear.

Methods: The colitis mice model was established by dextran sulfate sodium (DSS) treatment. Protein levels (p-STAT3/STAT3, ROR-γt, p-STAT5/STAT5, FOXP3, p-AMPK/AMPK, and p-mTOR/mTOR) were examined using Western blotting analysis. Changes in histopathology were detected through hematoxylin and eosin staining. The proportion of T helper 17 (Th17) cells and regulatory T (Treg) cells was measured by flow cytometry analysis.

Results: CTD1 improved body weight and colon length, and alleviated inflammation and histological damage in DSS-induced colitis mice model. DSS treatment also demonstrated a negative effect on Th17-Treg cells balance whereas CTD1 restored the balance of Th17- Treg cells in DSS-induced colitis mice model. Regulatory factors (such as STAT3, ROR-γt, STAT5, and FOXP3) that closely related to the balance of Th17-Treg cells were regulated by CTD1. In addition, AMPK phosphorylation was increased and mTOR phosphorylation was inhibited by CTD1 in DSS-induced colitis mice model.

Conclusion: These findings established that CTD1 improved DSS-induced colitis by suppressing Th17-Treg cells balance by activating the AMPK/mTOR pathway. This study provided a new strategy for developing novel treatments for patients with IBD.