Shengjiang Xiexin Decoction ameliorates DSS-induced ulcerative colitis via activating Wnt/β-Catenin signaling to enhance epithelium renovation and modulating intestinal flora

Phytomedicine. 2025 Apr:139:156456. doi: 10.1016/j.phymed.2025.156456. Epub 2025 Feb 1.

Abstract

Background: Shengjiang Xiexin Decoction (SJXXD) is a recognized formulation in traditional Chinese medicine that is commonly employed in diarrhea treatment. It has the potential to be a viable alternative for treating ulcerative colitis (UC), but its therapeutic effects and mechanisms remain unclear.

Purpose: This study aims to explore the effects and underlying mechanism of SJXXD in a mouse model of UC induced by dextran sulfate sodium (DSS).

Method: The components of SJXXD were analyzed using HPLC-Q/TOF-MS. UC mice model was established by freely drinking of 3% DSS, and SJXXD was administered as an intervention. After 7 days, body weight change, diarrhea, blood stools, colon length, cytokine levels, and key barrier proteins were evaluated to assess the therapeutic effect of SJXXD on UC. Additionally, transcriptome sequencing, quantitative polymerase chain reaction (qPCR), western blotting, intestinal organoids, 16S rRNA sequencing, and heat correlation analysis were employed to investigate the potential mechanisms of SJXXD on treating UC.

Results: SJXXD significantly inhibited weight loss, reduce diarrhea and bloody stools, lower disease activity index (DAI) score, suppressed inflammatory cell infiltration and cytokines secretion in colonic tissues in UC mice. Additionally, SJXXD also enhances the expression of tight junction and mucins. Transcriptome sequencing results indicate that SJXXD primarily activates the Wnt/β-Catenin pathway, thereby enhancing the expression of genes linked to intestinal stem cells and intestinal regeneration markers. At phylum level, SJXXD significantly increases the relative abundance of Verrucomicrobiota, while inhibiting Campylobacterota and Fusobacteriota. Importantly, the relative abundance of these bacterial phyla is significantly correlated with UC and Wnt/β-Catenin signaling pathway.

Conclusion: These results indicate that SJXXD can significantly treat DSS-induced mouse UC model by activating the Wnt/β-Catenin pathway and modulating intestinal flora. SJXXD may serve as a promising therapeutic approach for the management of UC.

Keywords: Epithelium renovation; Intestinal flora; Shengjiang Xiexin Decoction; Ulcerative colitis; Wnt/β-Catenin signaling.

MeSH terms

  • Animals
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / microbiology
  • Colon / drug effects
  • Dextran Sulfate
  • Disease Models, Animal
  • Drugs, Chinese Herbal* / pharmacology
  • Gastrointestinal Microbiome* / drug effects
  • Intestinal Mucosa / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Wnt Signaling Pathway* / drug effects

Substances

  • Drugs, Chinese Herbal
  • Dextran Sulfate