Inhibitory Effects of 7‐Carboxymethyloxy‐3′,4′,5‐Trimethoxy Flavone (DA‐6034) on Helicobacter pylori‐Induced NF‐κB Activation and iNOS Expression in AGS Cells

Abstract

The Helicobacter pylori were identified by Marshall and Warren in 1984. H. pylori survive in the forbidding harsh acid environment of the stomach and duodenum by hiding in the mucus layer and neutralizing gastric acid in its local surrounding environment. Multiple lines of evidence suggest that H. pylori infection is one of the primary causes of gastritis and peptic ulcer, which are provoked by oxidative stress and inflammation. More than 50% of the world's population is infected by this bacterium. The H. pylori-induced inflammation has been implicated in the pathogenesis and progression of gastric cancer. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone) is a synthetic flavonoid known to possess anti-inflammatory activity. It has been reported that oral administration of DA-6034 suppresses the inflammatory bowel disease (IBD) in animal models. In this article, we attempted to examine the effect of DA-6034 on H. pylori-induced inflammation in human gastric cancer (AGS) cells by targeting NF-kappaB and extracellular signal-regulated kinase (ERK), a representative MAPK.

A Comparative Study of Clinicopathological Features between Chronic Cholecystitis Patients with and without Helicobacter pylori Infection in Gallbladder Mucosa

“…In the pathogenesis of gastric cancer, H.pylori is proved to promote the expression of ROS/RNS mediated by NF-κB, AP-1 and other pathways. [39], [40] High concentration of NO can lead to nitrative DNA damage and canceration of the epithelium. [41] In our study, the expression levels of ROS and iNOS were significantly increased in H.pylori infected gallbladder mucosa than that in non-infected mucosa.…”

Comparative proteomics analysis of chronic atrophic gastritis: changes of protein expression in chronic atrophic gastritis without Helicobacter pylori infection

“…The results of some investigations on H. pylori have revealed that the PBP-RAF/MAPK and NF-κB pathways could be the crucial mechanism of the pathopoiesis of H. pylori . Fox and Wang (27), Shibata et al (28), and Lee et al (29) have confirmed that the induction of cytokines and chemokines and growth-related genes by H. pylori is mediated by the PBP-RAF/MAPK and NF-κB signaling pathways. In our molecular interaction network of CAG, the changes of PSME1 or RPS12 and the impact on the NF-κB and PBP-RAF/MAPK signaling pathways could be analogous to the reaction to H. pylori infection.…”

DA-6034 Induces [Ca2+]iIncrease in Epithelial Cells

“…The distribution of unbalanced redox can evoke inflammatory signaling pathway and apoptosis, such as NF-κB activation and inflammation [22,23]. DA-6034 suppressed iNOS induction, NF-κB activation, p65 nuclear translocation, and restored IκBα level in the cytoplasm and dissociates the IKK-γ-Hsp90 complex in gastric cancer models [11,12]. In addition, DA-6034 attenuated JNK and p38 MAPK and also inhibited NF-κB activation in dry eye model cells [15].…”

“…Eupatilin has also the pharmacological activities including the induction of apoptosis in both human gastric cancer cells and promyelocytic leukemia cells, and cell cycle arrest in ras -transformed human mammary epithelial cells [8,9]. DA-6034 has anti-inflammatory action through NF-κB down-regulation in gastric epithelial cells [10,11,12]. DA-6034 prevents gastric mucosal injury through increases of endogenous prostaglandin E 2 (PGE 2 ) synthesis and gastric mucus secretion [8].…”