Protective Effect of Gegen Qianliantang on Intestinal Mucosal Barrier in Ulcerative Colitis Mice via STAT3/NF-κB Axis Regulating Th1/Treg Differentiation
10.13422/j.cnki.syfjx.20250717
- VernacularTitle:从STAT3/NF-κB信号通路调控Th1/Treg分化探究葛根芩连汤对溃疡性结肠炎小鼠肠黏膜屏障的保护效应机制
- Author:
Beilei DENG
1
;
Anan WANG
2
;
Wenya FENG
2
;
Lixin WANG
3
;
Tiansong ZHANG
4
;
Chengyong MA
2
;
Xiutian GUO
1
Author Information
1. Shanghai University of Traditional Chinese Medicine（TCM）， Shanghai 201203， China
2. Jing'an District Hospital of TCM， Shanghai 200072， China
3. Shanghai Pulmonary Hospital Affiliated to Tongji University， Shanghai 200433， China
4. Jing'ann District Centre Hospital， Shanghai 200040， China
- Publication Type:Journal Article
- Keywords:
ulcerative colitis;
Gegen Qianliantang;
intestinal mucosal barrier function;
nuclear transcription factor（NF）-κB p65/signal transducer and activator of transcription 3（STAT3） signaling pathway;
CD4+ T cell subpopulation;
anti-inflammatory immune regulation
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(20):12-21
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the protective effect and mechanism of Gegen Qianliantang （GQT） on intestinal mucosal barrier function in dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） model mice. MethodsA UC model was established in C57BL/6 mice using a 2.5% DSS solution. Mice were randomly divided into five groups （n=8 per group）： blank group， model group， mesalazine sustained-release granule group （0.52 g·kg-1）， high-dose GQT group （2.23 g·kg-1）， and low-dose GQT group （1.12 g·kg-1）. Fecal characteristics and body weight changes were observed before and after treatment. The body weight loss and disease activity index （DAI） of UC mice were calculated to evaluate symptom severity. Hematoxylin-eosin （HE） staining and Alizarin blue-periodic acid-Schiff （AB-PAS） staining were used to detect histological changes in colon tissue. Immunohistochemistry was used to detect the expression of zonula occludens-1 （ZO-1） and mucin 2 （MUC2）. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pro-inflammatory cytokines interferon-γ （IFN-γ）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， IL-17A， and anti-inflammatory cytokine IL-10. Flow cytometry was used to detect the activation of helper T lymphocyte subsets （Th1， Th17）， regulatory T cells （Treg）， and regulatory B cells （Breg） in spleen and colon tissues. Western blot was used to detect the expression levels of T-bet， forkhead box protein P3（FoxP3）， nuclear transcription factor（NF）-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， signal transducer and activator of transcription 3（STAT3）， and phosphorylated STAT3 （p-STAT3）. ResultsCompared with the model group， both high- and low-dose GQT groups significantly improved the body weight loss and DAI scores （P<0.05）， alleviated colonic inflammation， and showed optimal efficacy in the high-dose group. AB-PAS staining showed that compared with the model group， both the high- and low-dose GQT groups significantly increased goblet cell proliferation and mucin secretion， indicating improved mucosal barrier function. GQT upregulated the expression of ZO-1 and MUC2 in colon tissue （P<0.05）， suppressed IFN-γ， IL-6， and TNF-α secretion （P<0.05）， elevated IL-10 secretion （P<0.05）， but had no significant effect on IL-17A. At the same time， high- and low-dose GQT intervention increased the activation of CD4+ FoxP3+ Treg cells （P<0.05） and suppressed activation of CD4+ IFN-γ+ Th1 cells （P<0.05）. Western blot showed that GQT downregulated T-bet， NF-κB p65， and STAT3 protein expression （P<0.05）， upregulated FoxP3 （P<0.05）， and also reduced phosphorylation levels of p-NF-κB p65 and p-STAT3 （P<0.05）. ConclusionGQT can upregulate the activation of CD4+ FoxP3+ Treg cells， reduce the activation of CD4+ IFN-γ+ Th1 cells， inhibit the secretion of IFN-γ， IL-6， and TNF-α， and increase the secretion of IL-10. It enhances the expression of MUC2 and ZO-1 in colon tissue， thereby alleviating inflammatory damage to the intestinal mucosa and restoring mucosal barrier integrity. These effects may be related to its regulation of NF-κB p65 and STAT3 signaling pathways， ultimately regulating the activation of transcription factors T-bet and FoxP3.
