Abstract

Helicobacter pylori (H. pylori) is a bacterium known to infect the human stomach. It can cause various gastrointestinal diseases including gastritis and gastric cancer. Hesperetin is a major flavanone component contained in citrus fruits. It has been reported to possess antibacterial, antioxidant, and anticancer effects. However, the antibacterial mechanism of hesperetin against H. pylori has not been reported yet. Therefore, the objective of this study was to determine the inhibitory effects of hesperetin on H. pylori growth and its inhibitory mechanisms. The results of this study showed that hesperetin inhibits the growth of H. pylori reference strains and clinical isolates. Hesperetin inhibits the expression of genes in replication (dnaE, dnaN, dnaQ, and holB) and transcription (rpoA, rpoB, rpoD, and rpoN) machineries of H. pylori. Hesperetin also inhibits the expression of genes related to H. pylori motility (flhA, flaA, and flgE) and adhesion (sabA, alpA, alpB, hpaA, and hopZ). It also inhibits the expression of urease. Hespereti n downregulates major virulence factors such as cytotoxin-associated antigen A (CagA) and vacuolating cytotoxin A (VacA) and decreases the translocation of CagA and VacA proteins into gastric adenocarcinoma (AGS) cells. These results might be due to decreased expression of the type IV secretion system (T4SS) and type V secretion system (T5SS) involved in translocation of CagA and VacA, respectively. The results of this study indicate that hesperetin has antibacterial effects against H. pylori. Thus, hesperetin might be an effective natural product for the eradication of H. pylori.

Highlights

  • Helicobacter pylori (H. pylori) is a Gram-negative, curved bacterium

  • cytotoxin-associated antigen A (CagA) protein was dramatically decreased by hesperetin treatment. These results indicate that hesperetin can reduce the translocation of CagA and vacuolating cytotoxin A (VacA) proteins into AGS cells and inhibit morphological changes such as hummingbird phenotype and vacuolation caused by H. pylori infection

  • These results indicate that hesperetin can reduce the translocation of CagA and VacA9 pofr1o7teins into AGS cells and inhibit morphological changes such as hummingbird phenotype and vacuolation caused by H. pylori infection

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Summary

Introduction

Helicobacter pylori (H. pylori) is a Gram-negative, curved bacterium. It is well known as an important human pathogen. H. pylori causes various gastrointestinal diseases such as gastritis, chronic gastritis, peptic ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma [1]. The prevalence of H. pylori varies widely depending on age, ethnicity, socioeconomic status, dietary habits such as food, alcohol consumption, and smoking status [2]. East Asian countries are at high risk of gastric cancer due to the high rates of H. pylori infection [3]. A concerted effort for the eradication of H. pylori infection is necessary for health promotion worldwide

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