Inhibitory Effects of Menadione on Helicobacter pylori Growth and Helicobacter pylori-Induced Inflammation via NF-κB Inhibition

Abstract

<i>H. pylori</i> is classified as a group I carcinogen by WHO because of its involvement in gastric cancer development. Several reports have suggested anti-bacterial effects of menadione, although the effect of menadione on major virulence factors of <i>H. pylori</i> and <i>H. pylori</i>-induced inflammation is yet to be elucidated. In this study, therefore, we demonstrated that menadione has anti-<i>H. pylori</i> and anti-inflammatory effects. Menadione inhibited growth of <i>H. pylori</i> reference strains and clinical isolates. Menadione reduced expression of <i>vac</i>A in <i>H. pylori</i>, and translocation of VacA protein into AGS (gastric adenocarcinoma cell) was also decreased by menadione treatment. This result was concordant with decreased apoptosis in AGS cells infected with <i>H. pylori</i>. Moreover, cytotoxin-associated protein A (CagA) translocation into <i>H. pylori</i>-infected AGS cells was also decreased by menadione. Menadione inhibited expression of several type IV secretion system (T4SS) components, including <i>vir</i>B2, <i>vir</i>B7, <i>vir</i>B8, and <i>vir</i>B10, that are responsible for translocation of CagA into host cells. In particular, menadione inhibited nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) activation and thereby reduced expression of the proinflammatory cytokines such as IL-1β, IL-6, IL-8, and TNF-α in AGS as well as in THP-1 (monocytic leukemia cell) cell lines. Collectively, these results suggest the anti-bacterial and anti-inflammatory effects of menadione against <i>H. pylori</i>.