Berberrubine inhibits <i>Helicobacter pylori</i> by inducing oxidative stress and impairing membrane integrity

<i>Helicobacter pylori</i> is a major gastric pathogen with increasing antibiotic resistance, creating an urgent need for new therapeutic strategies. We screened 37 pure compounds and 9 herbal extracts for anti-<i>H. pylori</i> activity and identified berberrubine as the most potent agent, with a minimum inhibitory concentration of 11 μg/ml. Berberrubine exhibited bacteriostatic effects by inducing oxidative stress and disrupting membrane integrity, as demonstrated by transcriptomic analysis, reactive oxygen species (ROS) accumulation, and structural damage, all of which were alleviated by the antioxidant N-acetylcysteine. Similar inhibitory effects were observed in <i>Escherichia coli</i>, indicating broader antimicrobial potential. This study provides the mechanistic evidence of berberrubine's activity against <i>H. pylori</i>, highlighting its promise as a candidate for development into alternative therapies to address antibiotic resistance.