Berberrubine Inhibits Helicobacter pylori by Inducing Oxidative Stress

Helicobacter pylori is a prevalent pathogen that colonizes the pylorus and contributes to the pathogenesis of gastric cancer. The increasing antibiotic resistance in H. pylori presents a substantial challenge for effective eradication, making the development of more effective therapeutic strategies imperative. In this study, we screened 37 pure compounds (purity >95%), 3 ethanol extracts, and 6 aqueous extracts from 6 different medicinal herbs for their potential inhibitory effects against H. pylori in vitro. Among the tested compounds, 15 exhibited inhibitory activity, with berberrubine demonstrating the strongest effect, characterized by a minimum inhibitory concentration (MIC) of 0.011 mg/ml. The comparative transcriptome analysis revealed a significant upregulation of the oxidative stress response related genes, such as fumC and sodB, in H. pylori treated with berberrubine. Further in vitro assays confirmed that berberrubine exerted antibacterial activity by stimulating oxidative stress, as evidenced by increased reactive oxygen species (ROS) production and impaired cell membrane integrity. Additionally, similar inhibitory tests were applied to Escherichia coli, a common gut opportunistic pathogen. The results showed that berberrubine inhibited E. coli through the same mechanism observed for H. pylori. In conclusion, berberrubine is a potent antibacterial agent against gastrointestinal pathogens, including H. pylori and E. coli, making it a promising candidate for further development as an antimicrobial therapeutic ImportanceThis study identified berberrubine as a potent antibacterial agent against gastrointestinal pathogens, including Helicobacter pylori and Escherichia coli by inducing cellular oxidative stress. Through increased reactive oxygen species (ROS) production and disruption of bacterial cell membrane integrity, berberrubine demonstrated strong efficacy in inhibiting drug-resistant pathogens. These findings highlight its potential as a promising therapeutic candidate for eradicating drug-resistant gastrointestinal pathogens.