Ginsan, an acidic
polysaccharide prepared from Panax ginseng, demonstrated multiple immunomodulatory effects in previous studies. This study was conducted to elucidate the
antiseptic mechanism induced by
ginsan in mice infected with Staphylococcus aureus. When mice were treated with
ginsan before the bacterial challenge with S. aureus, they were highly protected from
sepsis-induced death. The numbers of S. aureus recovered from
ginsan-treated mice were considerably lower than those recovered from nontreated mice. The in vivo depletion of monocytes/macrophages caused more S. aureus to be recovered from the bacteria-infected mice. Nevertheless, mice treated with both
etoposide and
ginsan were able to maintain an antibacterial activity. In addition, the phagocytic activity of
ginsan-treated macrophage against S. aureus was considerably enhanced. The synthesis of inflammatory
cytokines, such as
tumor necrosis factor-alpha interleukin (IL)-1beta,
IL-6, IFN-gamma,
IL-12,
IL-18 and
interferon gamma, was significantly downregulated at the early phase of
sepsis in mice that were treated with
ginsan before the bacterial challenge. Expression of
Toll-like receptors (TLRs), including TLR2, TLR4, and TLR9, as well as the adaptor molecule MyD88, was considerably reduced in peritoneal macrophages that were treated with
ginsan before a subsequent contact with S. aureus. These data indicated that
ginsan protected mice from S. aureus-induced
sepsis through the suppression of acute inflammatory responses at an early phase and the enhancement of antimicrobial activities at subsequent phases of
infection.