Ligustrazine Attenuates Gastric Inflammation and Apoptosis in Helicobacter pylori-induced Gastric Epithelial Cells

Abstract

Background: Stomach disorders, including gastric cancer and gastritis, are associated with the pathogenic bacterium Helicobacter pylori. Enhanced inflammation is the characteristic of H. pylori-induced gastritis. Ligustrazine exerts anti-inflammatory properties in mouse asthma models and acute kidney injury. Objectives: To determine the role of ligustrazine in H. pylori-induced gastritis. Methods: Normal gastric epithelial cell line (GES-1) was cultured with H. pylori at a multiplicity of infection (MOI) of 100: 1 for 24 hours. GES-1 cell line under H. pylori condition was incubated with 100 or 200 μM ligustrazine for 24 hours. Cell viability and apoptosis were investigated by MTT and flow cytometry assays, respectively. Inflammation was assessed by determining the levels and mRNA expression of interleukins (IL)-6/8, tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein 1 (MCP-1) using ELISA and qRT-PCR analysis, respectively. Results: Helicobacter pylori infection reduced the viability and promoted the apoptosis of GES-1 cell line, accompanied by the enhanced activities of caspases 3 and 9. However, ligustrazine reversed the H. pylori-induced infection decreased viability, while increased apoptosis and caspases 3/9 activities in GES-1 cell line. Moreover, ligustrazine attenuated H. pylori-induced secretions of pro-inflammatory factors, IL-6/8, TNF-α, and MCP-1, in GES-1 cell line. The protein expression of inhibitor of NF-κB (IκBα) was downregulated in GES-1 cell line after H. pylori infection, while the protein expression levels of p65 and phosphorylation of IκBα were upregulated by H. pylori infection. On the contrary, ligustrazine decreased H. pylori-induced protein expression of IκBα, whereas increased protein expression of p65 and phosphorylation of IκBα. Conclusions: Ligustrazine exerted protective effects on H. pylori-induced gastric epithelial cells through inhibition of gastric inflammation and apoptosis and inactivation of NF-κB pathway.