Fuente: PubMed "swarm" Naunyn Schmiedebergs Arch Pharmacol. 2026 Mar 28. doi: 10.1007/s00210-026-05247-3. Online ahead of print.ABSTRACTEscherichia coli (E. coli) led to increasingly severe issues of antimicrobial resistance, underscoring an urgent need for the development of novel antibacterial strategies. Gypenosides (GPs), the primary active constituents of the medicinal and edible plant Gynostemma pentaphyllum, possess a variety of pharmacological activities, including anti-inflammatory and immunomodulatory effects. However, their antibacterial mechanisms against E. coli remain unclear. Therefore, this study integrated network pharmacology, molecular docking, molecular dynamics simulations, and in vitro experiments to elucidate the antibacterial mechanism of GPs from the dual perspective of the host and the pathogen. The results indicated that network pharmacology analysis identified 72 common targets, among which STAT3, MTOR, AKT1, HSP90AA1, ESR1, and IL6 were predicted as core regulatory nodes. Molecular docking and molecular dynamics simulations confirmed that GP XLIX, the main active component of GPs, exhibit stable binding ability to targets such as IL6, with its binding site located in the peripheral region of the IL6 receptor-binding epitope (Site I). In vitro experiments demonstrated that at inhibitory concentrations, GPs disrupt the integrity of the bacterial cell membrane, and even at sub-inhibitory concentrations, they significantly inhibit bacterial swarming motility, revealing a multi-target, systemic antibacterial profile. In summary, GPs possess the dual potential for direct antibacterial action and host-mediated indirect effects, providing a theoretical foundation for the development of antibacterial agents based on natural products and their application in the food and biomedical fields.PMID:41902853 | DOI:10.1007/s00210-026-05247-3