5-hydroxy-6-8-11-14-eicosatetraenoic-acid and Helicobacter-Infections

Our recent studies documented that red ginseng extract (RGE, isolates from steamed and dried Panax ginseng, C.A. Meyer) can inhibit Helicobacter pylori-induced mitogen-activated protein kinase (MAPK) signaling with repressing either nuclear factor (NF)-kappaB-DNA binding activity or releases of IL-8 and COX-2 in gastric epithelial cells (Dig Dis Sci 50:1218-1227, 2005). We extended the experiment to prove whether RGE influences 5-lipoxygenase (5-LOX) pathway, thereby suppressing the biosynthesis of 5(S)-HETE. The 5-LOX enzyme activities were measured by thin layer chromatography using (14)C-labeled arachidonic acid (AA) and quantified by reverse phase-high performance liquid chromatography in human gastric adenocarcinoma (AGS) cells cocultured with H pylori (ATCC 43504 strain) with or without pretreatment of RGE. Western blotting analyses for MAPK signaling and 5-LOX, reverse transcriptase polymerase chain reaction for interleukin-8, and electrophoretic mobility shift assay for NF-kappaB-DNA binding were done, respectively. H pylori infection increased exclusively 5-LOX enzyme activity and RGE inhibited H pylori-stimulated 5-LOX activity, resulting in suppression of 5(S)-HETE generations from AA. RGE inactivated c-jun phosphorylation and repressed redox-sensitive transcriptional activation, led to reduced expression of IL-8 and 5-LOX mRNA in gastric mucosal cells, of which action was very similar to known LOX inhibitor, 200 mumol of geraniin. RGE could be phytoceutical against H pylori infection-associated gastric inflammation through its LOX-inhibiting actions, inhibitory 5-LOX enzyme activity, and attenuating its expression.

Topics: Adenocarcinoma; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Cyclooxygenase 2; Epithelial Cells; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Hydroxyeicosatetraenoic Acids; Lipoxygenase Inhibitors; Mitogen-Activated Protein Kinases; Panax; Plant Extracts; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Stomach Neoplasms; Tumor Cells, Cultured