Authors
Shu-Ya Wu, Bei-Bei Dong, Qian-Yin Xue, Jing-Yu Xu, Yi Zhang, Hao-Meng Wu, Hai-Qing Ao
Published in
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. Volume 51. Issue 13. Pages 3841-3850.
Abstract
This study investigated the mechanism by which Xiaoyao San ameliorates "brain-gut" interaction disorders in chronic stress-induced mice by examining its effects on T helper 1 cell(Th1)/T helper 2 cell(Th2) immune balance. Forty male C57BL/6 mice(6-8 weeks old, SPF grade) were randomly assigned to four groups(n=10 per group): control group, model group, Xiaoyao San group(7.63 g·kg~(-1)), and fluoxetine hydrochloride group(4.11 mg·kg~(-1)). Except for the control group, all groups underwent 28 days of chronic unpredictable mild stress(CUMS) to establish the model. Behavioral tests were conducted on day 28. From day 29, the Xiaoyao San and fluoxetine hydrochloride groups received corresponding drug solutions via oral gavage for 28 days(once daily), while the control and model groups received equivalent volumes of saline. CUMS modeling continued uninterrupted during the administration period. Behavioral assessments were repeated on day 56, with body weight monitored throughout the experiment. Hematoxylin-eosin(HE) staining was used to observe pathological changes in intestinal tissues. The villus height and crypt depth were measured, and their ratio was calculated. Immunohistochemistry(IHC) was employed to detect the expression of tight junction proteins zonula occludens-1(ZO-1) and occludin in the intestinal mucosa. Serum levels of interferon-γ(IFN-γ), interleukin(IL)-2, IL-4, IL-10, corticosterone(CORT), gastrin(GAS), motilin(MTL), and somatostatin(SS) were measured using enzyme-linked immunosorbent assay(ELISA) and subjected to correlation analysis. Western blot was performed to assess T-box transcription factor T-bet and GATA-binding protein 3(GATA-3) protein expression in the hypothalamus and intestinal tissues. The results demonstrated that Xiaoyao San significantly alleviated CUMS-induced depressive-like behaviors, including weight loss, reduced sucrose preference, and decreased locomotor activity in the open field test. HE staining indicated that Xiaoyao San effectively restored intestinal villus structure and increased the villus height-to-crypt depth ratio. IHC results showed that Xiaoyao San enhanced the expression of occludin and ZO-1 related to intestinal mucosal barrier, suggesting improved intestinal barrier function. ELISA analysis revealed that Xiaoyao San significantly decreased serum levels of CORT, SS, IFN-γ, and IL-2, while increasing GAS, MTL, IL-4, and IL-10, indicating mitigation of stress-induced damage and inflammatory responses, as well as regulation of brain-gut peptide secretion. Western blot results showed that Xiaoyao San significantly reduced T-bet protein expression and the T-bet/GATA-3 ratio in both the hypothalamus and intestinal tissues, suggesting correction of Th1/Th2 immune imbalance induced by CUMS. Correlation analysis indicated significant associations between brain-gut peptides and Th1/Th2-related inflammatory factors, implying a link between Th1/Th2 inflammatory responses and brain-gut regulatory function. In conclusion, Xiaoyao San ameliorates brain-gut interaction disorders in chronic stress mice, potentially through restoring Th1/Th2 immune balance, attenuating inflammatory responses, and modulating "brain-gut" peptide secretion.
PMID:
42543374
Bibliographic data and abstract were imported from PubMed on 03 Aug 2026.
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