A natural product Ginsenoside C-K with Antimicrobial Activity against Streptococcus pneumoniae.

Streptococcus pneumoniae is a major cause of bacteremia and sepsis, and rising antimicrobial resistance necessitates new therapies. This study aimed to screen ginsenosides with antipneumococcal activity and to evaluate antibacterial effects of candidate compound. Among nine ginsenosides tested in vitro, only Ginsenoside C-K exhibited significant antibacterial activity with a minimum inhibitory concentration (MIC) of 4-8 µg·mL-1. Further investigation demonstrated that Ginsenoside C-K exerted rapid bactericidal effects and effectively inhibited both the formation and stability of biofilms. In addition, it disrupted bacterial membrane integrity and induced the accumulation of reactive oxygen species (ROS). Moreover, Ginsenoside C-K treatment of S. pneumoniae-infected cells was associated with the restoration of mitochondrial membrane potential and reduced expression of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β. In vivo, treatment with Ginsenoside C-K significantly improved the survival rate of infected hosts to 60%-70%. In summary, Ginsenoside C-K exhibits potent antimicrobial activity both in vitro and in vivo, combining antibacterial, antibiofilm, and antiinflammatory effects. This study provides new experimental evidence supporting the application of ginsenoside-derived natural products in the treatment of pneumococcal infections and offers valuable insight for the development of novel antimicrobial lead compounds.