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Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 5: 998 - 1008

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.05.007

Original Articles

Effect of Chang’an decoction (肠安方) on ulcerative colitis by regulating T helper 17 cells and regulatory T cells via Rab27 in the p53/high mobility group box 1 pathway

  • Li ZHENG ,
  • Ting JIN ,
  • Xiaojing WANG ,
  • Yingqi WANG ,
  • Fengbin LIU ,
  • Hong MI
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  • 1 the First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
    2 Department of Gastroenterology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China
    3 Department of Gastroenterology, Baiyun Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China
    4 Lingnan Medical Research Centre, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

Received date: 2024-08-22

  Accepted date: 2025-01-12

  Online published: 2025-09-15

Supported by

Lingnan Medical Research Center of Guangzhou University of Chinese Medicine;National Natural Science Foundation of China: Mechanism of Chang’an Decoction in Intestinal Mucosal Immunity of Ulcerative Colitis on Exocrine Mediated Rab27(81903963);Natural Science Foundation of Guangdong Province: the Role of the Neuropeptide Spexin-associated Gycogen Synthase Kinase-3β Signaling Pathway in Regulating the Enteric Nervous-immune Network in Ulcerative Colitis and the Intervention Mechanism of Chang’an Formula(2018A030310614)

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Abstract

OBJECTIVE: To explore the effect of Chang’an decoction (肠安方, CAD) of ameliorating the immune imbalances in ulcerative colitis (UC) by regulating Rab27 in the P53/high mobility group box 1 pathway.

METHODS: The functions and important signaling pathways of the Rab27- and UC-related genes were analyzed viathe use of microarray data from the gene expression omnibus database, gene ontology database, Kyoto encyclopedia of genes and genomes database and gene set enrichment analysis. Dextran sulfate sodium salt-induced colitis mouse model was used to verify the bioinformatics results. Colon length, body weight, and disease activity index were measured. Hematoxylin and eosin staining was applied to validate the histopathology. Tight junction proteins were detected by immunohistochemistry. The proportions of T helper 17 cells (Th17) and regulatory T cells (Treg) in mesenteric lymph nodes were measured viaflow cytometry. Proinflammatory cytokines like interleukin (IL) 17 (IL-17), IL-21 and IL-22 and anti-inflammatory cytokines like transforming growth factor β and IL-10 in the serum and colon of mice were detected by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction, respectively. The expression levels of high mobility group box 1 (HMGB1), P53 and phospho- P53 (P-P53) in colonic tissues were detected by immunofluorescence and Western blotting.

RESULTS: Bioinformatics analysis revealed that compared with normal tissues, the expression of Rab27 was significantly increased in UC tissues. Receiver operating characteristic curve showed that Rab27 has the potential to be used as a biomarker for the diagnosis of disease activity. Enrichment analysis showed that UC and Rab27 were mainly associated with small molecule transport, nutrient metabolism, transmembrane transport and the downstream pathway of P53. According to animal experiments, the expression of Rab27 was increased in UC tissues, which aggravated the colonic pathological damage, activated the expression of HMGB1, and also leaded to the imbalance of Th17 and Treg cells. After CAD intervention, Rab27 overexpression, weight loss, colon shortening, and pathological damage were substantial reduced, the expression of tight junction proteins, zona occludens 1 and Occludin were increased. The effect of CAD at high-dose was more obvious. In addition, CAD upgraded the number of Treg cells and the production of TGF-β and IL-10, while decreasing the number of Th17 cells and the expression of inflammatory cytokines (IL-17, IL-21, and IL-22). Moreover, colon inflammation was alleviated by CAD, as indicated by the regulation of HMGB1 and P-P53 expression.

CONCLUSION: The expression of Rab27, HMGB1 and P-P53 could be decreased by CAD, and the balance of Th17 and Treg cells as well as their related cytokines could be regulated by CAD.

Key words： ulcerative colitis; Rab27; high mobility group box 1; T helper 17 cells; regulatory T cells; bioinformatics; Chang’an decoction

Cite this article

Li ZHENG , Ting JIN , Xiaojing WANG , Yingqi WANG , Fengbin LIU , Hong MI . Effect of Chang’an decoction (肠安方) on ulcerative colitis by regulating T helper 17 cells and regulatory T cells via Rab27 in the p53/high mobility group box 1 pathway[J]. Journal of Traditional Chinese Medicine, 2025 , 45(5) : 998 -1008 . DOI: 10.19852/j.cnki.jtcm.2025.05.007

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