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

• Published in: Allergologia et immunopathologia Vol. 50; no. 5; pp. 153 - 161
• Main Authors: Yang, Ying Xue, Yuan, Yuan, Xia, Boning
• Format: Journal Article
• Language: English; Spanish
• Published: Murcia Codon Publications 01.01.2022
• Subjects: Antibodies; Colon; Edema; Flow cytometry; Inflammation; Inflammatory bowel disease; Kinases; Laboratory animals; Lymphatic system; Medical research; Proteins; Software; Statistical analysis; Transcription factors; Tumor necrosis factor-TNF; Variance analysis; United States > US; China
• ISSN: 0301-0546; 0301-0546; 1578-1267
• DOI: 10.15586/aei.v50i5.654

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 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) 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.