Anti-inflammatory Effect of Capsaicin in Helicobacter pylori-Infected Gastric Epithelial Cells

Background and aim: Capsaicin, the main pungent ingredient of hot red and chilli pepper, has been considered as not only a cytoprotective but also a detrimental agent to the gastric mucosa. However, the effect and mechanism of capsaicin that modulate the induction of pro‐inflammatory cytokine in Helicobacter pylori‐infected epithelial cells have not been investigated previously. Herein, we demonstrated that capsaicin inhibited the release of pro‐inflammatory cytokine, interleukin‐8 (IL‐8) by H. pylori‐infected gastric epithelial cells through nuclear factor‐κB (NF‐κB) signal pathway. Materials and methods: AGS or MKN45 cells as gastric epithelial cells and Vac A+, CagA+ wild‐type H. pylori strain ATCC 49503 were used. Gastric epithelial cells were pre‐treated with various concentrations of capsaicin and infected with H. pylori for different periods of time to determine IL‐8 concentrations in culture supernatant by an ELISA assay. We measured IL‐8 mRNA transcripts in H. pylori‐infected gastric epithelial cells co‐treated with capsaicin by reverse transcriptase‐polymerase chain reaction analysis. We performed electrophoretic mobility shift assay to examine the NF‐κB DNA binding activity with capsaicin and immunofluorescence microscopy to examine nuclear staining of p65. We also performed immunoblotting for IκB, IKK activity with capsaicin. Results: Capsaicin inhibits H. pylori‐induced IL‐8 production by gastric epithelial cells in dose‐ and time‐dependent manner. Capsaicin as low as 100 µmol/L significantly inhibited IL‐8 production in H. pylori‐infected MKN45 cells (43.2% of control) at 24 hours incubation, whereas inhibited IL‐8 production in H. pylori‐infected AGS cells (70% of control). We confirmed that capsaicin inhibited IL‐8 mRNA expression after infection of gastric epithelial cells with H. pylori for 6 hours. The addition of capsaicin (100 µmol/L) suppressed H. pylori‐induced NF‐κB activation in gastric epithelial cells at 1 hour post‐infection. We also found that the degradation of IκB and IKK activation were inhibited by capsaicin. Conclusions: Nontoxic dose of capsaicin inhibited H. pylori‐induced IL‐8 production by gastric epithelial cells through the modulation of IκB‐, NF‐κB‐, and IL‐8 pathways. We conclude that capsaicin can be proposed as a potential anti‐inflammatory drug by inhibition of the production of IL‐8 in H. pylori‐infected gastric epithelium.