Antiviral Activity of Fermented Ginseng Extracts against a Broad Range of Influenza Viruses.

Ginseng products used as herb nutritional supplements are orally consumed and fermented to ginsenoside compounds by the intestinal microbes. In this study, we investigated antiviral protective effects of fermented ginseng extracts against different strains of influenza viruses in genetically diverse mouse models. Intranasal coinoculation of mice with fermented ginseng extract and influenza virus improved survival rates and conferred protection against H1N1, H3N2, H5N1, and H7N9 strains, with the efficacy dependent on the dose of ginseng samples. Antiviral protection by fermented ginseng extract was observed in different genetic backgrounds of mice and in the deficient conditions of key adaptive immune components (CD4, CD8, B cell, MHCII). The mice that survived primary virus inoculation with fermented ginseng extract developed immunity against the secondary infection with homologous and heterosubtypic viruses. In vitro cell culture experiments showed moderate virus neutralizing activity by fermented ginseng extract, probably by inhibiting hemagglutination and neuraminidase activity. This study suggests that fermented ginseng extracts might provide a means to treat influenza disease regardless of virus strains.

Heat-killed Lactobacillus casei confers broad protection against influenza A virus primary infection and develops heterosubtypic immunity against future secondary infection.

Lactic acid bacteria (LAB) are the common probiotics. Here, we investigated the antiviral protective effects of heat-killed LAB strain Lactobacillus casei DK128 (DK128) on influenza viruses. Intranasal treatment of mice with DK128 conferred protection against different subtypes of influenza viruses by lessening weight loss and lowering viral loads. Protection via heat-killed DK128 was correlated with an increase in alveolar macrophage cells in the lungs and airways, early induction of virus specific antibodies, reduced levels of pro-inflammatory cytokines and innate immune cells. Importantly, the mice that were protected against primary viral infection as a result of heat-killed DK128 pretreatment developed subsequent heterosubtypic immunity against secondary virus infection. For protection against influenza virus via heat-killed DK128 pretreatment, B cells and partially CD4 T cells but not CD8 T cells were required as inferred from studies using knockout mouse models. Our study provides insight into how hosts can be equipped with innate and adaptive immunity via heat-killed DK128 treatment to protect against influenza virus, supporting that heat-killed LAB may be developed as anti-virus probiotics.

Ginseng protects against respiratory syncytial virus by modulating multiple immune cells and inhibiting viral replication.

Ginseng has been used in humans for thousands of years but its effects on viral infection have not been well understood. We investigated the effects of red ginseng extract (RGE) on respiratory syncytial virus (RSV) infection using in vitro cell culture and in vivo mouse models. RGE partially protected human epithelial (HEp2) cells from RSV-induced cell death and viral replication. In addition, RGE significantly inhibited the production of RSV-induced pro-inflammatory cytokine (TNF-α) in murine dendritic and macrophage-like cells. More importantly, RGE intranasal pre-treatment prevented loss of mouse body weight after RSV infection. RGE treatment improved lung viral clearance and enhanced the production of interferon (IFN-γ) in bronchoalveolar lavage cells upon RSV infection of mice. Analysis of cellular phenotypes in bronchoalveolar lavage fluids showed that RGE treatment increased the populations of CD8+ T cells and CD11c+ dendritic cells upon RSV infection of mice. Taken together, these results provide evidence that ginseng has protective effects against RSV infection through multiple mechanisms, which include improving cell survival, partial inhibition of viral replication and modulation of cytokine production and types of immune cells migrating into the lung.

Ginseng diminishes lung disease in mice immunized with formalin-inactivated respiratory syncytial virus after challenge by modulating host immune responses.

Formalin-inactivated respiratory syncytial virus (FI-RSV) immunization is known to cause severe pulmonary inflammatory disease after subsequent RSV infection. Ginseng has been used in humans for thousands of years due to its potential health benefits. We investigated whether ginseng would have immune modulating effects on RSV infection in mice previously immunized with FI-RSV. Oral administration of mice with ginseng increased IgG2a isotype antibody responses to FI-RSV immunization, indicating T-helper type 1 (Th1) immune responses. Ginseng-treated mice that were nonimmunized or previously immunized with FI-RSV showed improved protection against RSV challenge compared with control mice without ginseng treatment. Ginseng-mediated improved clinical outcomes after live RSV infection were evidenced by diminished weight losses, decreased interleukin-4 cytokine production but increased interferon-γ production, modulation of CD3 T-cell populations toward a Th1 response, and reduced inflammatory response. Ginseng-mediated protective host immune modulation against RSV pulmonary inflammation was observed in different strains of wild-type and mutant mice. These results indicate that ginseng can modulate host immune responses to FI-RSV immunization and RSV infection, resulting in protective effects against pulmonary inflammatory disease.