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 dis-ease, including ulcerative colitis (UC) and Crohn’s disease (CD), which is typically charac-terized by chronicity and relapse. Cinnamtannin D1 (CTD1), extracted from Cinnamomum tamala, 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) treat-ment. 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 histopathol-ogy 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 suppress-ing Th17–Treg cells balance by activating the AMPK/mTOR pathway. This study provided a new strategy for developing novel treatments for patients with IBD (AU)