Metformin Inhibits the Development of Helicobacter pylori-Associated Gastritis by Regulating the ERK-MMP10-IL-1β Axis.

Abstract

Helicobacter pylori infection is one of the most common factors inducing gastric mucosal inflammation. Upon infecting gastric epithelial cells, H. pylori generates reactive oxygen species (ROS), which act as inducers of matrix metalloproteinases (MMPs). ROS can regulate MMP gene expression and promote their production through the ERK signaling pathway, with MMP-10 being a primary MMP induced during H. pylori infection. By mediating the remodeling of the gastric epithelial and lamina propria layers, MMP-10 enhances H. pylori colonization and its pro-inflammatory effects. As resistance to eradication therapies has significantly increased, H. pylori eradication rates have continued to decline. We investigated the antioxidant effects of metformin on cell viability, migration, and invasion. The in vitro levels of ROS, MMP-10, and the inflammatory factor IL-1β in H. pylori-infected gastric epithelial cells were assessed to determine whether metformin could alleviate H. pylori-induced inflammation and elucidate its potential mechanisms of action. These findings may provide novel insights into adjunctive therapeutic strategies for the effective clinical eradication of H. pylori infection. The results indicated that H. pylori infection significantly increased ROS production, activating the ERK pathway and upregulating MMP-10 expression, which enhanced cellular invasion and the inflammatory response. Metformin intervention effectively blocked this pathological cascade, significantly reducing ROS levels, MMP-10 expression, and the release of inflammatory cytokines, exerting an inhibitory effect on H. pylori-induced inflammation and demonstrating the potential application of metformin as a therapeutic agent.