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Kynurenine Attenuates Ulcerative Colitis Mediated by the Aryl Hydrocarbon Receptor
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-13 , DOI: 10.1021/acs.jafc.4c04933
Caihong Wang 1 , Qihao Xu 1 , Chaozhi Wei 2 , Qinglian Hu 1 , Yingping Xiao 3 , Yuanxiang Jin 1, 2
Affiliation  

The higher prevalence of ulcerative colitis (UC) and the side effects of its therapeutic agents contribute to finding novel treatments. This study aimed to investigate whether kynurenine (KYN), a tryptophan metabolite, has the possibility of alleviating UC and further clarifying the underlying mechanism. The effect of KYN on treating UC was evaluated by intestinal pathology, inflammatory cytokines, and tight-junction proteins in colitis mice and LPS-stimulated Caco-2 cells. Our results revealed that KYN relieved pathological symptoms of UC, improved intestinal barrier function, enhanced AhR expression, and inhibited NF-κB signaling pathway activation in the colon of colitis mice. Moreover, the improved intestinal barrier function, the decreased inflammasome production, and the inhibited activation of the NF-κB signaling pathway by KYN were dependent on AhR in Caco-2 cells. KYN could trigger AhR activation, inactivate the NF-κB signaling pathway, and inhibit NLRP3 inflammasome production, thus alleviating intestinal epithelial barrier dysfunction and reducing intestinal inflammation. In conclusion, the present study reveals that KYN ameliorates UC by improving the intestinal epithelial barrier and activating the AhR-NF-κB-NLRP3 signaling pathway, and it can be a promising therapeutic agent and dietary supplement for alleviating UC.

中文翻译:


犬尿氨酸减轻芳基烃受体介导的溃疡性结肠炎



溃疡性结肠炎(UC)的较高患病率及其治疗药物的副作用有助于寻找新的治疗方法。本研究旨在探讨色氨酸代谢物犬尿氨酸(KYN)是否具有缓解UC的可能性,并进一步阐明其潜在机制。通过结肠炎小鼠和 LPS 刺激的 Caco-2 细胞的肠道病理学、炎症细胞因子和紧密连接蛋白来评估 KYN 对治疗 UC 的作用。我们的结果表明,KYN 可缓解结肠炎小鼠结肠中的 UC 病理症状,改善肠道屏障功能,增强 AhR 表达,并抑制 NF-κB 信号通路激活。此外,Caco-2 细胞中肠道屏障功能的改善、炎症小体产生的减少以及 KYN 对 NF-κB 信号通路激活的抑制均依赖于 AhR。 KYN可以触发AhR激活,失活NF-κB信号通路,抑制NLRP3炎症小体的产生,从而缓解肠上皮屏障功能障碍,减轻肠道炎症。总之,本研究表明,KYN 通过改善肠上皮屏障和激活 AhR-NF-κB-NLRP3 信号通路来改善 UC,并且它可以成为缓解 UC 的有前景的治疗剂和膳食补充剂。
更新日期:2024-09-13
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