A mechanism for the action of the compound DA-6034 on NF-κB pathway activation in Helicobacter pylori-infected gastric epithelial cells.

DA-6034 is a synthetic derivative of eupatilin, a flavonoid with anti-inflammatory effects. The aim of this study was to investigate the effects of DA-6034 on the interactions between IκB kinase (IKK) and heat shock protein 90 (Hsp90), and activation of the nuclear factor-kappaB (NF-κB) signalling pathway in human gastric epithelial cells infected with Helicobacter pylori. MKN-45 gastric epithelial cell line was treated with DA-6034 and H. pylori. DA-6034 significantly inhibited NF-κB activation and upregulated the expressions of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 in MKN-45 cells infected with H. pylori. However, DA-6034 did not influence activator protein-1 DNA binding activity in H. pylori-infected gastric epithelial cells. Pretreatment with DA-6034 attenuated the H. pylori-induced increase in IKK activity, and Hsp90 was associated with IKK-α and IKK-γ in MKN-45 cells. Treatment with DA-6034 dissociated the Hsp90 and IKK-γ complex in H. pylori-infected cells, leading to the inhibition of IL-8 expression. These results suggest that the eupatilin derivative 7-carboxymethyloxy-3',4',5-trimethoxy flavone has anti-inflammatory activity in gastric epithelial cells infected with H. pylori through the promotion of the dissociation of the IKK-γ-Hsp90 complex and suppression of NF-κB signalling.