Chishizhi Yuyuliang Decoction Ameliorates Ulcerative Colitis in Mice by Promoting Colonic Epithelial Mucosal Healing via the CAV1/FA Axis

  • Rapid Commun Mass Spectrom. 2026 Aug 30;40(16):e70106. doi: 10.1002/rcm.70106.
Xing Hong  1 ,  Yuxin Wen  1  2 ,  Benjiang Xiao  1 ,  Qi Jiang  3 ,  Meng Chen  3 ,  Pengyu Chen  3 ,  Rui Qian  3 ,  Qiong Wang  3 ,  Jingjing Li  3 ,  Fang Huang  1 ,  Zhuang Huang  1 ,  Lintao Han  3  4  5
Affiliations
  • 1. College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
  • 2. Public Inspection and Testing Center of Xianning, Xianning, China.
  • 3. Key Laboratory of Traditional Chinese Medicine Resources and Chemistry of Hubei Province, Wuhan, China.
  • 4. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
  • 5. School of Basic Medical Science, Hubei University of Chinese Medicine, Wuhan, China.
PMID: 42200545 DOI: 10.1002/rcm.70106
Abstract

Objective: This study aimed to investigate the therapeutic mechanisms of CY in treating UC using an integrated metabolomics and proteomics approach.

Methods: A murine UC model was induced using dextran sulfate sodium (DSS). The therapeutic efficacy of CY was evaluated via histological examination (H&E staining) of colon tissues to assess inflammation, epithelial necrosis, and crypt abscesses. Serum and colon tissues were collected for ELISA, immunofluorescence, Western blotting, metabolomics, and proteomics analyses. Additionally, an in vitro intestinal epithelial barrier model was established using LPS-induced Caco-2 cells. Cell viability, barrier function (TEER and FITC-Dextran permeability), cell damage (LDH), and inflammatory cytokine levels (IL-6 and IL-1β) were measured. The expression and distribution of tight junction proteins (ZO-1 and occludin) and signaling proteins (FAK, p-FAK, paxillin, and p-paxillin) were analyzed via immunofluorescence and Western blotting.

Results: CY treatment significantly reduced the Disease Activity Index (DAI) and suppressed the levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in UC mice. Proteomic analysis identified Caveolin-1 (CAV1) and the focal adhesion pathway as key therapeutic targets and signaling pathways. Metabolomic profiling revealed 17 endogenous metabolites, highlighting tryptophan metabolism and butyrate metabolism as critical pathways. Furthermore, CY intervention modulated arachidonic acid and linoleic acid metabolism. Mechanistically, CY upregulated the expression of CAV1 and FAK while downregulating Akt and paxillin phosphorylation. In vitro experiments demonstrated that CY-containing serum restored the barrier function of LPS-induced Caco-2 cells by regulating FAK/paxillin phosphorylation, upregulating tight junction proteins, and mitigating inflammatory responses.

Conclusion: CY involvement in colonic mucosal healing attenuates inflammation and enhances intestinal barrier function in DSS-induced colitis, likely through the modulation of the CAV1/FA axis. These findings provide a theoretical basis for the clinical application of CY and offer novel insights for the development of therapeutic agents for UC.

Keywords
CAV1; Chishizhi Yuyuliang decoction; focal adhesion; metabolomics; proteomics; ulcerative colitis.
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