Enhanced anti-ESKAPE pathogen and antibiofilm activities of Korean red ginseng-derived silver nanoparticles via membrane deformation: LC/HRMS profiling and dynamic correlations

Red Ginseng is widely recognized for its diverse pharmacological activities, which are largely attributed to its ginsenoside content. A commercial processed Korean Red Ginseng extract product (HO3), hereafter referred to as “HO3 extract”, was used throughout this study. HO3 extract was analyzed using LC-HR-MS to evaluate and profile its ginsenoside content. LC-HR-MS analysis tentatively identified six major ginsenosides, namely Rh1, Rh2, Rg1, Rg2, Rg3, and Rb1. Subsequently, silver nanoparticles (AgNPs) incorporating HO3 extract were synthesized and analyzed using transmission electron microscopy (TEM), Fourier transform infrared (FTIR), spectroscopy ultraviolet–visible (UV–Vis) spectroscopy, scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta potential measurements, energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD) analysis. The synthesized AgNPs exhibited a characteristic absorption band at 420 nm, indicating nanoparticle formation, while FTIR analysis revealed the presence of functional groups involved in nanoparticle stabilization. The antibacterial and antibiofilm activities of HO3 extract and HO3-mediated AgNPs were subsequently evaluated. Antibacterial assessment demonstrated that AgNPs significantly outperformed HO3 extract, exhibiting higher inhibition percentages and lower minimum inhibitory concentration (MIC) values against both Gram-negative and Gram-positive pathogens. Furthermore, biofilm inhibition assays revealed markedly greater suppression by AgNPs (55–75%) than by HO3 extract (7–16%), with the highest activity observed against Pseudomonas aeruginosa. Time-kill assays further demonstrated that the antibacterial efficacy of AgNPs was both dose- and time-dependent. Moreover, the identified major ginsenosides were subjected to molecular dynamics (MD) simulations against microbial membrane models to predict their potential antimicrobial mechanisms. Notably, ginsenosides Rg1 and Rb1 exhibited the strongest membrane-disruptive effects, inducing substantial bilayer thinning and reducing local membrane thickness, thereby supporting their potential antimicrobial role.