Transcriptomics and network pharmacology reveal the molecular mechanisms through which leonurine protects against...

Leonurine has been demonstrated to exert significant therapeutic effects against Salmonella enteritidis induced intestinal inflammation; however, its precise mechanism of action in combating Salmonella infection remains unclear. In this study, a Salmonella infection IEC6 cell model was established to evaluate the efficacy of leonurine in combating Salmonella infection using CCK8, cytopathic effect (CPE) analysis, immunofluorescence, transmission electron microscopy (TEM), and flow cytometry. Subsequent integration of network pharmacology, transcriptomics, and molecular docking revealed potential targets and signaling pathways, which were further validated by RT-qPCR and Western blotting. Immunofluorescence and TEM revealed that leonurine effectively inhibited bacterial invasion and intracellular proliferation. Flow cytometry and CPE assays demonstrated its ability to alleviate cellular damage and inhibit apoptosis. The integrated network pharmacology transcriptomics molecular docking analysis revealed robust interactions between leonurine and PTGS2, PARP1, and mTOR. Mechanistic validation confirmed that leonurine inhibits Salmonella invasion via the modulation of tight junction proteins and restricts intracellular bacterial proliferation by regulating ferroptosis and autophagy signaling pathways. This study reveals the potential targets and molecular mechanisms through which leonurine combats Salmonella infection, providing a scientific foundation for the prevention and control of salmonellosis.