Effect of daphnetin, the coumarin derivative isolated from Daphne genus, on Helicobacter pylori adhesion to gastric epithelial cells.

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL Phytomedicine Pub Date : 2025-02-01 Epub Date: 2024-12-29 DOI:10.1016/j.phymed.2024.156357

Genzhu Wang, Mengjie Wang, Jing Pang, Qiang Sun, Tianyun Fan, Zhongdong Li, Xuefu You

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Abstract

Background: Adherence of Helicobacter pylori to the surface of the gastric mucosa is the initial and crucial step for its survival and colonization in the harsh conditions of the stomach. We had previously demonstrated that daphnetin has anti-adhesion effect.

Purpose: This study aims to explore the mechanisms of daphnetin to reduce H. pylori adhesion to gastric epithelial cells (GES-1).

Methods: Fluorescence microscopy and urease assay were used to observe and validate the anti-adhesion effect of daphnetin. Terminal deoxynucleotidyl transferase dUTP nick end labeling, comet assay and agarose gel-based assay were conducted to evaluate the level of DNA damage. Quantitative real-time polymerase chain reaction, western blotting, electrophoretic mobility shifts assay and enzyme-linked immunosorbent assay were performed to investigate the mechanisms of the anti-adhesion effect of daphnetin.

Results: Our results showed that daphnetin decreased H. pylori adhesion to GES-1 in time- and dose-dependent manners. The mechanisms by which daphnetin inhibits H. pylori adhesion involved the inducing of DNA double-strand breaks, the up-regulating of recA transcription leading to RecA binding at 1018-1597 site in the babA promoter, the decreasing of babA/babB transcription ratio, the decreasing of BabA expression and its interaction with Lewis b antigen.

Conclusion: Our results suggested that daphnetin significantly inhibits H. pylori adhesion to GES-1 through the RecA-BabA pathway. To our knowledge, this is the first report on the mechanisms of daphnetin affecting H. pylori adhesion to GES-1.

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达芙妮属香豆素衍生物瑞香素对幽门螺杆菌粘附胃上皮细胞的影响。

背景：幽门螺杆菌在胃粘膜表面的粘附是其在恶劣的胃条件下生存和定植的初始和关键步骤。我们之前已经证明了瑞香素具有抗粘连作用。目的：探讨瑞香素降低幽门螺杆菌粘附胃上皮细胞（GES-1）的作用机制。方法：采用荧光显微镜和脲酶法观察并验证瑞香素的抗黏附作用。采用末端脱氧核苷酸转移酶dUTP缺口末端标记法、彗星法和琼脂糖凝胶法评价DNA损伤水平。采用实时定量聚合酶链反应、western blotting、电泳迁移率转移、酶联免疫吸附等方法研究瑞香素抗黏附作用的机制。结果：我们的研究结果显示，瑞香素降低幽门螺杆菌对GES-1的粘附呈时间和剂量依赖性。瑞香素抑制幽门螺杆菌粘附的机制包括诱导DNA双链断裂、上调recA转录导致recA在babA启动子1018-1597位点结合、降低babA/babB转录比、降低babA表达及其与Lewis b抗原的相互作用。结论：我们的研究结果表明，瑞香素通过RecA-BabA途径显著抑制幽门螺杆菌对GES-1的粘附。据我们所知，这是关于瑞香素影响幽门螺杆菌粘附GES-1机制的第一篇报道。

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

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.