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Berberine Alleviates Citrobacter rodentium-Induced Colitis with Reduced Epithelial Gasdermin E-Mediated Pyroptosis
Meiqi Zhang1, Sixian Wei2, Zheng Luo2
1School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.
International Journal of Molecular Sciences
|August 13, 2026
Summary
Berberine from Coptis chinensis shows promise in treating colitis. This traditional Chinese medicine component reduces intestinal cell death and inflammation, offering a potential new therapy for inflammatory bowel disease (IBD).
Area of Science:
- Pharmacology
- Gastroenterology
- Immunology
Background:
- Inflammatory bowel disease (IBD) presents significant challenges due to costly and adverse treatments.
- Traditional Chinese medicine, like Coptis chinensis, offers potential therapeutic alternatives for intestinal inflammation.
- The specific active components and mechanisms of Coptis chinensis in alleviating colitis remain largely undefined.
Purpose of the Study:
- To identify active alkaloid components in Coptis chinensis that inhibit epithelial cell death and reduce colitis.
- To elucidate the molecular mechanisms underlying the anti-inflammatory and cytoprotective effects of these compounds.
- To evaluate the therapeutic efficacy of a lead compound in an in vivo model of infectious colitis.
Main Methods:
- Screening of Coptis chinensis alkaloids in a TNF-α/cycloheximide-induced epithelial cell death model.
- Assessment of pyroptosis markers (caspase-3, GSDME cleavage), HMGB1 release, MAPK signaling (ERK, JNK), and inflammatory gene expression via Western blotting and qPCR.
- In vivo evaluation in a Citrobacter rodentium-induced colitis model, assessing disease severity, histopathology, bacterial load, and barrier function markers.
Main Results:
- Berberine (BBR) demonstrated potent cytoprotective activity, significantly reducing epithelial cell death and pyroptosis.
- BBR inhibited HMGB1 release, attenuated ERK and JNK phosphorylation, and downregulated pro-inflammatory gene expression in vitro.
- In vivo, BBR ameliorated colitis symptoms and histopathological damage, enhanced intestinal barrier markers (Tjp1, Muc2), and reduced GSDME cleavage, without significantly altering bacterial burden.
Conclusions:
- Berberine is identified as a key active component of Coptis chinensis with significant anti-colitis properties.
- BBR exerts its therapeutic effects by modulating epithelial pyroptosis, likely through GSDME pathway inhibition.
- Berberine represents a promising therapeutic candidate for infectious colitis and potentially other forms of IBD involving epithelial pyroptosis.
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