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

Abstract

H. pylori 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 H. pylori and H. pylori-induced inflammation is yet to be elucidated. In this study, therefore, we demonstrated that menadione has anti-H. pylori and anti-inflammatory effects. Menadione inhibited growth of H. pylori reference strains and clinical isolates. Menadione reduced expression of vacA in H. pylori, 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 H. pylori. Moreover, cytotoxin-associated protein A (CagA) translocation into H. pylori-infected AGS cells was also decreased by menadione. Menadione inhibited expression of several type IV secretion system (T4SS) components, including virB2, virB7, virB8, and virB10, 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 H. pylori.

Effects of sodium butyrate supplementation on inflammation, gut microbiota, and short‐chain fatty acids in Helicobacter pylori‐infected mice

“…However, TLR2 (but not TLR4) has been reported as essential for H. pylori ‐induced NF‐κB activation and chemokine expression by epithelial cells 37 . Chronic gastritis is induced by H. pylori infection through virulence factors, such as CagA and VacA, which induce the NF‐κB signaling pathway by activating inflammatory factors, including IL‐8 and TNF‐α 5,38 . Our results revealed that H. pylori significantly increased the phosphorylation of the NF‐κB p65 subunit as well as the degradation and phosphorylation of IκBα, which was similar to previous reports 39 .…”

“…Chronic inflammation is considered an important inducer of tumor development. H. pylori induces gastric epithelial inflammation through different virulence factors, such as cytotoxin‐associated protein A (CagA), vacuolating cytotoxin A (VacA) and lipopolysaccharide (LPS), and induces NF‐κB nuclear translocation and IL‐8 production 5,6 …”

Probiotic effect on Helicobacter�pylori attachment and inhibition of inflammation in human gastric epithelial cells

“…Pro-inflammatory cytokine production occurs during H. pylori infection, with the inflammatory reactions potentially leading to chronic inflammation rather than eliminating H. pylori (38,39). The transcription factor NF-κB can be activated by IL-1β, LPS, peptidoglycan and tumor necrosis factor-α during H. pylori infection (40). NF-κB is critical modulator of cytokine expression (41).…”

Rice Protein Exerts Anti-Inflammatory Effect in Growing and Adult Rats via Suppressing NF-κB Pathway

“…Upon activation of NF-κB, the transcription of a number of inflammatory genes can be activated, e.g., tumor necrotic factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), monocyte chemoattractant protein-1 (MCP-1), etc. [1,[16][17][18][19]. This is the basic functional mechanism through which the NF-κB transcription factor induces an inflammatory response.…”