Daphnetin: A Novel Anti-Helicobacter pylori Agent

被引：34

作者：

Wang, Genzhu ^{[1
,2
]}

Pang, Jing ^{[1
,2
]}

Hu, Xinxin ^{[1
,2
]}

Nie, Tongying ^{[1
,2
]}

Lu, Xi ^{[1
,2
]}

Li, Xue ^{[1
,2
]}

Wang, Xiukun ^{[1
,2
]}

Lu, Yun ^{[1
,2
]}

Yang, Xinyi ^{[1
,2
]}

Jiang, Jiandong ^{[1
,2
]}

Li, Congran ^{[1
,2
]}

Xiong, Yan Q. ^{[3
,4
]}

You, Xuefu ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Inst Med Biotechnol, Beijing Key Lab Antimicrobial Agents, Beijing 100050, Peoples R China

[2] Peking Union Med Coll, Beijing 100050, Peoples R China

[3] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Helicobacter pylori; daphnetin; mechanism of action; colonization; ANTIBIOTIC-RESISTANCE; GASTRIC EPITHELIUM; CELLS; SUSCEPTIBILITY; ACTIVATION; INFECTION; ROS;

D O I：

10.3390/ijms20040850

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Antibiotic-resistant H. pylori was increasingly found in infected individuals, which resulted in treatment failure and required alternative therapeutic strategies. Daphnetin, a coumarin-derivative compound, has multiple pharmacological activities. Methods: The mechanism of daphnetin on H. pylori was investigated focusing on its effect on cell morphologies, transcription of genes related to virulence, adhesion, and cytotoxicity to human gastric epithelial (GES-1) cell line. Results: Daphnetin showed good activities against multidrug resistant (MDR) H. pylori clinical isolates, with minimal inhibitory concentration (MIC) values ranging from 25 to 100 g/mL. In addition, daphnetin exposure resulted in H. pylori morphological changes. Moreover, daphnetin caused increased translocation of phosphatidylserine (PS), DNA damage, and recA expression, and RecA protein production vs. control group. Of great importance, daphnetin significantly decreased H. pylori adhesion to GES-1 cell line vs. control group, which may be related to the reduced expression of colonization related genes (e.g., babA and ureI). Conclusions: These results suggested that daphnetin has good activity against MDR H. pylori. The mechanism(s) of daphnetin against H. pylori were related to change of membrane structure, increase of DNA damage and PS translocation, and decrease of H. pylori attachment to GES-1 cells.

引用

页数：13

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