Fuxing Li , Shujia Song , Mingming Huang , Yaxing Xu , Bingxiang Zhao , Zhenlin Liu , Bin Fu , Huilai Zhang , Hanying Zou , Min Zhou , Lihua Li , Xiaobo Wang
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引用次数: 0
Abstract
Ulcerative colitis (UC) is a chronic relapsing non-transmural inflammatory bowel disease characterized by bloody diarrhea, closely associated with intestinal epithelial cell senescence and chronic inflammation. This study reveals novel mechanisms of the imidazole antifungal drug Miconazole (MCZ) in UC treatment. Through compound library screening, we found that MCZ effectively inhibits dextran sulfate sodium (DSS)-induced senescence in colonic epithelial NCM460 cells. Although clinically used for over 40 years, its anti-senescence and anti-inflammatory mechanisms remain unclear. Experiments confirmed that MCZ significantly reduces DSS-induced SA-β-Gal-positive cell proportion and P16/P21 expression. In animal models, MCZ ameliorated DSS-induced weight loss, bloody stools, and colonic tissue damage. Mechanistic studies demonstrated that MCZ specifically modulates microbiota composition (enriching beneficial bacteria Adlercreutzia, Lactobacillus, Ligilactobacillus, and Limosilactobacillus, while suppressing the relative abundance of Mycoplasma, Oscillibacter, and Streptococcus), and inhibits inflammatory progression by blocking the phosphorylation cascade of the NF-κB signaling pathway. These findings not only reveal MCZ's novel anti-senescence and anti-inflammatory functions but also provide potential new strategies for UC treatment.
期刊介绍:
Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products.
Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged.
Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.