甘草黄酮B是一种从甘草渣中提取的异戊二烯类黄酮,可通过重建肠道屏障和调节肠道菌群来缓解葡聚糖硫酸钠诱导的溃疡性结肠炎

IF 4.2 3区 医学 Q1 PHARMACOLOGY & PHARMACY European journal of pharmacology Pub Date : 2022-02-05 DOI:10.1016/j.ejphar.2021.174730
Juan Zhang , Xiaoqin Xu , Ning Li , Li Cao , Yu Sun , Junchi Wang , Shuaibing He , Jianyong Si , Degang Qing
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引用次数: 13

摘要

溃疡性结肠炎(UC)是一种世界性的主要炎症性疾病。我们之前已经证明,甘草残黄酮(LFs)对UC的治疗效果令人满意。因此,研究LFs的成分可能会导致新的抗uc靶点的发现。本研究将licoflavone B (LB)从LFs中分离出来,给药于暴露于葡聚糖硫酸钠(DSS)的C57BL/6小鼠14天。我们的研究结果表明,高剂量LB (120 mg/kg)可显著预防dss诱导的体重减轻、疾病活动指数(DAI)升高、组织损伤和结肠炎症,表明LB对UC具有改善作用。我们还研究了肠道屏障和微生物群的组成,试图探索LB对抗UC的机制。结果,我们发现LB通过抑制结肠细胞凋亡和保护occludin、claudin-1和ZO-1的表达来保持结肠屏障的完整性。此外,LB通过抑制有害细菌(肠球菌等)和促进有益微生物(拟杆菌等)来重塑菌群组成。进一步的分子研究表明,LB通过阻断MAPK通路发挥抗uc活性。本研究首次探讨了LB的抗uc活性,并阐明了其作用机制。这些结果将为发现新的抗uc药物提供有价值的线索。
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Licoflavone B, an isoprene flavonoid derived from licorice residue, relieves dextran sodium sulfate-induced ulcerative colitis by rebuilding the gut barrier and regulating intestinal microflora

Ulcerative colitis (UC) is a major inflammatory disease worldwide. We previously demonstrated that licorice residue flavones (LFs) showed satisfactory efficacy in the treatment of UC. Therefore, research into the ingredients of LFs may lead to the discovery of novel anti-UC targets. In the current study, we separated licoflavone B (LB) from LFs and administered it to dextran sodium sulfate (DSS)-exposed C57BL/6 mice for 14 days. Our results demonstrated that high dose LB (120 mg/kg) significantly prevented DSS-induced weight loss, disease activity index (DAI) increase, histological damage, and colonic inflammation, indicating that LB has ameliorative effects on UC. We also investigated the composition of the intestinal barrier and microflora in an attempt to explore the mechanisms of LB against UC. As a result, we found that LB preserved the integrity of the colonic barrier by inhibiting colonic cell apoptosis and protecting the expression of occludin, claudin-1, and ZO-1. Moreover, LB reshaped the microflora composition by suppressing harmful bacteria (Enterococcus et al.) and boosting beneficial microorganisms (Bacteroides et al.). Further molecular exploration implied that LB exerted anti-UC activity through blocking the MAPK pathway. Here, we explored anti-UC activity of LB for the first time and clarified its mechanisms. These results will provide valuable clues for the discovery of novel anti-UC agents.

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来源期刊
CiteScore
9.00
自引率
0.00%
发文量
572
审稿时长
34 days
期刊介绍: The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.
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