Korean Red Ginseng Extract Inhibits IL-8 Expression via Nrf2 Activation in Helicobacter pylori-Infected Gastric Epithelial Cells.

Hae Sou Kim,Hyeyoung Kim,Joo Weon Lim

doi:10.3390/nu14051044

Abstract

Helicobacter pylori (H. pylori) causes gastric diseases by increasing reactive oxygen species (ROS) and interleukin (IL)-8 expression in gastric epithelial cells. ROS and inflammatory responses are regulated by the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of Nrf2 target genes, superoxide dismutase (SOD) and heme oxygenase-1 (HO-1). We previously demonstrated that Korean red ginseng extract (RGE) decreases H. pylori-induced increases in ROS and monocyte chemoattractant protein 1 in gastric epithelial cells. We determined whether RGE suppresses the expression of IL-8 via Nrf2 activation and the expression of SOD and HO-1 in H. pylori-infected gastric epithelial AGS cells. H. pylori-infected cells were treated with RGE with or without ML385, an Nrf2 inhibitor, or zinc protoporphyrin (ZnPP), a HO-1 inhibitor. Levels of ROS and IL-8 expression; abundance of Keap1, HO-1, and SOD; levels of total, nuclear, and phosphorylated Nrf2; indices of mitochondrial dysfunction (reduction in mitochondrial membrane potential and ATP level); and SOD activity were determined. As a result, RGE disturbed Nrf2–Keap1 interactions and increased nuclear Nrf2 levels in uninfected cells. H. pylori infection decreased the protein levels of SOD-1 and HO-1, as well as SOD activity, which was reversed by RGE treatment. RGE reduced H. pylori-induced increases in ROS and IL-8 levels as well as mitochondrial dysfunction. ML385 or ZnPP reversed the inhibitory effect of RGE on the alterations caused by H. pylori. In conclusion, RGE suppressed IL-8 expression and mitochondrial dysfunction via Nrf2 activation, induction of SOD-1 and HO-1, and reduction of ROS in H. pylori-infected cells.

Highlights

Helicobacter pylori (H. pylori) infection is associated with atrophic gastritis, which can result in peptic ulcers or gastric cancer [1]
We previously showed that H. pylori induces the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to produce reactive oxygen species (ROS) in gastric epithelial cells [2]
superoxide dismutase (SOD)-2 levels were not affected by ML385 treatment. These results show that red ginseng extract (RGE) increased the levels of heme oxygenase-1 (HO-1) and SOD-1, which may be mediated by the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) in H. pylori-stimulated cells

Summary

Introduction

Helicobacter pylori (H. pylori) infection is associated with atrophic gastritis, which can result in peptic ulcers or gastric cancer [1]. We previously showed that H. pylori induces the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to produce reactive oxygen species (ROS) in gastric epithelial cells [2]. Oxidative stress contributes to the development of H. pylori-associated gastric diseases [3]. H. pylori-induced ROS cause an increase in the levels of inflammatory cytokines, including those of interleukin (IL)-8 [4]. IL-8 recruits inflammatory cells, neutrophils, and basophils to sites of infection, resulting in the propagation of inflammation. This can stimulate the subsequent production of ROS [5–7]. Uncontrolled production of ROS can impair mitochondrial function [8]

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