Nobiletin Regulates Gut Microbiota and Mediates HIF-1α to Alleviate DSS-Induced Ulcerative Colitis by Inhibiting Ferroptosis.

IF 5.7 1区农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY

Journal of Agricultural and Food Chemistry Pub Date : 2025-07-21 DOI:10.1021/acs.jafc.5c03076

Zhuosi Chen,Guoxin Huang,Guixuan Fang,Wenjian Wang,Feiyu Lan,Xinxun Lin,Mixian Deng,Tanxuan Huang,Tianli Lai,Lianxiang Luo

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Abstract

While nobiletin (NOB), a polymethoxy flavonoid, shows therapeutic potential for various disorders, its efficacy in ulcerative colitis (UC) management remains unexplored. This study aims to elucidate novel molecular targets of NOB and decipher its mechanistic underpinnings in UC treatment. Through complementary cellular models and dextran sulfate sodium (DSS) induced UC in mice models, we systematically revealed that NOB ameliorates UC symptoms through ferroptosis suppression. Comprehensive analyses identified HIF-1α as a principal target interacting with NOB. Notably, 16S rRNA sequencing demonstrated NOB's remarkable capacity to remodel gut microbiota (GM) composition, characterized by enrichment of beneficial microbial taxa and depletion of pathogenic species. Collectively, our findings reveal that NOB exerts therapeutic effects against UC through dual mechanisms: HIF-1α-mediated ferroptosis inhibition and GM modulation synergistically restore colonic mucosal barrier integrity. This study provides the first evidence positioning NOB as a promising multitarget therapeutic agent for UC management.

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诺比列素调节肠道菌群并通过抑制铁下垂介导HIF-1α减轻dss诱导的溃疡性结肠炎。

虽然nobiletin (NOB)，一种多甲氧基类黄酮，显示出治疗多种疾病的潜力，但其在溃疡性结肠炎（UC）治疗中的功效仍未被探索。本研究旨在阐明NOB的新分子靶点，并破译其在UC治疗中的机制基础。通过互补细胞模型和葡聚糖硫酸钠（DSS）诱导的UC小鼠模型，我们系统地揭示了NOB通过抑制铁下垂来改善UC症状。综合分析发现HIF-1α是与NOB相互作用的主要靶点。值得注意的是，16S rRNA测序显示NOB具有显著的重塑肠道微生物群（GM）组成的能力，其特征是有益微生物类群的富集和致病物种的减少。总之，我们的研究结果表明，NOB通过双重机制对UC发挥治疗作用：hif -1α介导的铁上吊抑制和GM调节协同恢复结肠粘膜屏障完整性。本研究首次提供证据，将NOB定位为UC治疗中有前景的多靶点治疗剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Agricultural and Food Chemistry 农林科学-农业综合

CiteScore

9.90

自引率

8.20%

发文量

1375

审稿时长

2.3 months

期刊介绍： The Journal of Agricultural and Food Chemistry publishes high-quality, cutting edge original research representing complete studies and research advances dealing with the chemistry and biochemistry of agriculture and food. The Journal also encourages papers with chemistry and/or biochemistry as a major component combined with biological/sensory/nutritional/toxicological evaluation related to agriculture and/or food.