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Berberine alleviates experimental colitis by enhancing gut-microbiota-dependent intestinal barrier function and suppressing gasdermin D activation
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DOI：10.3748/wjg.v32.i13.115299.png)
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Abstract
En 中文
BACKGROUND Ulcerative colitis (UC) is a chronic, recurrent inflammatory disease of the gastrointestinal tract that often presents challenges in clinical management. Traditional Chinese medicine constitutes a significant therapeutic modality for the management of UC. Berberine has demonstrated remarkable therapeutic potential for the treatment of UC. AIM To determine whether berberine alleviates dextran sulfate sodium (DSS)-induced UC in mice by enhancing gut microbiota-dependent intestinal barrier function and inhibiting gasdermin D (GSDMD) activation. METHODS An acute colitis mouse model was established by administering 3% DSS. The mice were treated daily with berberine (50 mg/kg and 100 mg/kg), after which body weight, colon length, histological scoring, and intestinal levels of inflammatory cytokines were assessed. Intestinal barrier permeability was evaluated, and 16S ribosomal RNA sequencing was conducted. Fecal microbiota transplantation and cohousing studies were performed to determine the role of the gut microbiota. The inhibitory effects of GSDMD were pharmacologically manipulated to substantiate the efficacy and underlying mechanism of action of berberine in treating UC in preclinical models. RESULTS Berberine has shown significant potential for alleviating the severity of DSS-induced acute colitis. Fecal microbiota transplantation and cohousing experiments showed that the gut microbiota is indispensable for the beneficial effects of berberine in DSS-induced colitis. Moreover, pharmacological inhibition of GSDMD attenuated the therapeutic efficacy of berberine, highlighting the importance of GSDMD in the mechanism of action. CONCLUSION Berberine alleviates experimental colitis by inhibiting the GSDMD-mediated pathway and increasing gut barrier function via a microbiota-mediated approach, thus offering a new molecular target for colitis therapy.
Keywords:
Ulcerative colitis
Berberine
Gasdermin D
Intestinal inflammation
Intestinal microbiota
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