Anti-inflammatory effects of eupatilin on Helicobacter pylori CagA-induced gastric inflammation

by Bong Eun Lee, Su Jin Park, Gwang Ha Kim, Dong Chan Joo, Moon Won Lee

Background

Eupatilin, a flavone isolated from Artemisia species, exerts anti-inflammatory, anti-oxidative, and anti-neoplastic activities. However, the effects of eupatilin on H. pylori-associated gastritis remain unclear. Thus, this study aimed to investigate the anti-inflammatory effects of eupatilin on gastric epithelial cells infected with cytotoxin-associated gene A (CagA)-positive Helicobacter pylori.

Materials and methods

AGS human gastric carcinoma cells were infected with a CagA-positive H. pylori strain and then treated with 10, 50, or 100 ng of eupatilin. After 24 h, the expression levels of CagA, phosphoinositide 3-kinase 1 (PI3K), nuclear factor (NF)-κB, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in the cell lysates were measured using western blotting, and the mRNA levels of IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1 were measured using real-time polymerase chain reaction.

Results

CagA translocation into AGS cells resulted in an elongated cell morphology, which was significantly suppressed by eupatilin treatment in a dose-dependent manner. Immunofluorescence staining for anti-CagA showed that eupatilin treatment dose-dependently inhibited CagA expression in the H. pylori-infected AGS cells. H. pylori infection increased the levels of pro-inflammatory cytokines including IL-1β, TNF-α, IL-6, IL-8, and MCP-1, and eupatilin treatment significantly reduced the levels of these cytokines in a dose-dependent manner. Additionally, eupatilin treatment dose-dependently suppressed the expression of PI3K and NF-κB.

Conclusions

Eupatilin treatment demonstrated anti-inflammatory effects on CagA-positive H. pylori-infected gastric epithelial cells by inhibiting CagA translocation, thereby suppressing the NF-κB signaling pathway. These results suggest that eupatilin plays a protective role against CagA-positive H. pylori-induced gastritis.