Qingchang suppository ameliorates mucosal inflammation in ulcerative colitis by inhibiting the differentiation and effector functions of Th1 and Th17 cells

• Published in: Journal of ethnopharmacology Vol. 337; no. Pt 2; p. 118865
• Main Authors: Cao, Hui, Liu, Huosheng, Dai, Xiaoling, Shi, Bei, Yuan, Jianye, Shan, Jingyi, Lin, Jiang
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 30.01.2025
• Subjects: Adult; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; blood; Cell Differentiation - drug effects; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - immunology; Colitis, Ulcerative - pathology; colon; colorectal neoplasms; Cytokines - metabolism; Differentiation and effector functions; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - pharmacology; Female; flow cytometry; fluorescent antibody technique; Humans; immunoblotting; immunohistochemistry; inflammation; interleukin-17; Interleukin-17 - metabolism; Intestinal Mucosa - drug effects; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; JNK signaling; Male; Middle Aged; mucosa; Oriental traditional medicine; phosphorylation; QCS; Suppositories; Th1 and Th17 cells responses; Th1 Cells - drug effects; Th1 Cells - immunology; Th17 Cells - drug effects; Th17 Cells - immunology; ulcerative colitis; Young Adult; QCS; JNK signaling; Th1 and Th17 cells responses; Differentiation and effector functions; UC
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2024.118865

Qing Chang Suppository (QCS), a traditional Chinese medicine formula, has been shown to effectively alleviate mucosal inflammation in patients with ulcerative colitis (UC). While the mechanism of QCS appears to be related to the regulation of CD4+T cell subset responses, direct evidence demonstrating that QCS inhibits Th1 and Th17 cell activation in UC (particularly based on human data) remains lacking. Additionally, the precise mechanisms through which QCS affects these cells have yet to be fully elucidated. This study aimed to investigate the effects of QCS on Th1 and Th17 cell responses in UC and to explore the underlying mechanisms. Twenty-eight patients with mild-to-moderate UC were recruited and treated with QCS for 12 weeks. Symptoms were assessed every two weeks, with sigmoidoscopies performed at baseline and at week 12. Intestinal mucosal biopsies and peripheral blood (PB) were collected at these time points. At the end of the trial, patients were categorized into responder and non-responder groups based on a modified Mayo disease activity index score. Healthy controls (HCs) were defined as subjects without IBD or colorectal carcinoma but with colon polyps. The frequencies of IFN-γ+CD4+T cells and IL-17A+CD4+T cells in PB and colonic mucosa were measured using flow cytometry. The expression levels and localization of T-bet, RORγT, IFN-γ, TNF-α, and IL-17A were determined via immunofluorescence, and JNK signaling activation was assessed through immunoblotting and immunohistochemistry. All parameters were compared across the three groups. At week 12, responders showed a significant reduction in colonic mucosal inflammation compared to baseline, accompanied by decreased frequencies of IFN-γ+CD4+T and IL-17A+CD4+ T cells in both PB and the colonic epithelial layer. Notably, Th1 and Th17 cell activity around intestinal epithelial cells (IECs) was nearly undetectable, as evidenced by the diminished expression of T-bet, RORγT, IFN-γ, TNF-α, and IL-17A. Additionally, JNK phosphorylation in these cells was significantly reduced. In contrast, non-responders exhibited no meaningful improvement; colonic pathology remained unchanged, and elevated levels of IFN-γ+CD4+T and IL-17A+CD 4+T cells persisted in both the PB and colonic epithelial layer. The presence of Th1 and Th17 cells and their associated cytokines around IECs remained substantial, and there was no significant change in JNK activation. QCS attenuates mucosal inflammation in UC patients by inhibiting the differentiation and effector functions of Th1 and Th17 cells, primarily through the regulation of the JNK signaling pathway. [Display omitted] •Mucosal Inflammation may be caused by Th1 and Th17 cells in ulcerative colitis.•Qingchang Suppository ameliorates mucosal Inflammation through suppressing Th1 and Th17 cell activation.•Qingchang Suppository inhibits Th1 and Th17 cell activation via the JNK signaling pathway.