The immunomodulator ginsan induces resistance to experimental sepsis by inhibiting Toll‐like receptor‐mediated inflammatory signals

Abstract

Ginsan, a polysaccharide extracted from Panax ginseng, has multiple immunomodulatory effects. In this study, we show that pretreatment of ginsan (25 lg/kg) protected mice from lethality induced by Staphylococcus aureus challenge. This survival benefit was associated with enhanced bacterial clearance from circulation, spleen and kidney. The phagocytic activity of macrophages treated with ginsan was significantly enhanced against S. aureus. However, the production of proinflammatory cytokines, such as TNFa, IL-1b, IL-6, IFN-c, IL-12, and IL-18, was markedly down-regulated in ginsan-treated mice compared with those of control-infected mice. The expression of Toll-like receptor (TLR) 2 and the adaptor molecule MyD88, which was greatly increased in septic macrophages, was significantly reduced by ginsan treatment in vitro. Similarly, the expression of phospho-JNK1/2, phospho-p38 MAPK, and NF-jB was decreased in the same culture system. These results illustrate that the antiseptic activity of ginsan can be attributed to enhanced bacterial clearance, and reduced proinflammatory cytokines via the TLR signaling pathway.

Toll-like receptor ligand-induced activation of murine DC2.4 cells is attenuated by Panax notoginseng

“…If so, this medicinal herb might be expected to benefit individuals infected with microbial pathogens by limiting the production of inflammatory mediators such as TNF-α and IL-6 without affecting the generation of pathogen-specific adaptive immunity. This possibility is consistent with a previous report demonstrating that notoginseng-treated mice were less susceptible to the ill effects of experimental sepsis, effects which the authors attributed to a decreased inflammatory response to infection (Ahn et al, 2006).…”

Protective Effect of Korean Red Ginseng Extract on the Infections by H1N1 and H3N2 Influenza Viruses in Mice

“…These limited nonspecific protective effects are consistent with results from previous studies demonstrating that pretreatment with ginseng polysaccharide showed survival advantages against experimental bacterial sepsis. 25,26 Ginseng treatment after infection showed lesser protective effects compared with those before infection. Consistent with our study, it was previously reported that saponins from ginseng extract suppressed the delayed-type hypersensitivity responses to the H1N1 influenza A/WSN virus when administered to the animals before but not after virus sensitization.…”

“…41 Also, time-dependent effects of treatment with ginseng (or ginseng polysaccharides) were observed previously. 24,26 In clinical studies, the incidence of common cold symptom complex or acute respiratory infection was also significantly lower in healthy individuals who had preventively taken ginseng. 29,42 The results in this study support the protective effects of ginseng against influenza virus infection when taken in healthy individuals.…”

“…The nature of these activities and their underlying mechanisms remain largely unknown and were reported to be diverse depending on types of diseases and/or biological assessment methods: some studies demonstrated anti-inflammatory activities, while others reported proinflammatory effects. [22][23][24][25][26] Previous clinical studies demonstrated the beneficial effects of ginseng intake. A group of older adults who received daily oral administration of ginseng and influenza virus vaccination showed fewer cases of laboratory-confirmed influenza-like illness compared with the vaccination-only group.…”

Chinese Medicine and Biomodulation in Cancer Patients—Part Two

“…Polysaccharide extracts from Panax ginseng can increase immunity and enhance chemotherapy [129][130][131] . There is evidence of interaction with TLRs, especially TLR4 136,137,148 .…”