Lee DK, et al. Clin Exp Vaccine Res. 2020 Jan;9(1):48-55. https://doi.org/10.7774/cevr.2020.9.1.48

Developing antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a global goal since the Coronavirus Disease 2019 (COVID-19) pandemic emerged in 2019. Korean Red Ginseng (KRG), recognized for its immunomodulating and antiviral properties, may be effective against SARS-CoV-2. Therefore, we aimed to investigate the efficiency of KRG in a human angiotensin-converting enzyme 2 (hACE2)-expressing mouse model infected with pseudo-typed SARS-CoV-2 (PSV). The lung injury score was assessed using H&E staining, and the immune cell population shift in the lung and spleen was observed through flow cytometry. Serum IgM and IgG concentrations were quantified using enzyme-linked immunoassay (ELISA). Pro-inflammatory cytokine levels were measured by cytometric bead assay (CBA) and polymerase chain reaction (PCR). Additionally, the expression of NLR family pyrin domain containing 3 (NLRP3) and inflammation-related transcription factors was detected by immunoblotting. RNA-sequencing and antibody array assays reconfirmed gene expression in inflammation and oxidation. KRG extract was most effective in treating lung injuries and serum IgM and IgG levels. Also, immune cells, including neutrophils, were regulated in the lungs, and tumor necrosis factor-alpha (TNF-a) levels were reduced. NLRP3 and phosphorylated nuclear factor-κB (NF-kB) and activator protein 1 (AP-1) were downregulated. Heme oxygenase-1 (HO-1) expression was increased, indicating that KRG extract has antioxidant properties. RNA-sequencing and antibody array assays revealed that KRG extract regulates the expression of genes associated with inflammation and oxidative damage. This study demonstrates that KRG extract may suppress PSV-induced inflammation and oxidative stress, making it a viable antiviral functional food.

And design: This research was conducted to investigate the immunomodulatory and anti-inflammatory effects of Korean red ginseng in a low-dose pseudo-type SARS-CoV-2 (PSV) infection model using hACE2 transgenic mice. K18-hACE2 transgenic mice were used as an experimental model, and three different Korean red ginseng formulations (non-saponin, saponin, and whole Korean red ginseng extract) were administered prior to infection with the virus. The physiological and immunological effects of the Korean red ginseng formulations were assessed by monitoring lung histopathology and luciferase activity in lung tissue. Flow cytometry was used to analyze the populations of immune cells in both the lungs and spleen, and serum IgM levels were quantified using an enzyme-linked immunosorbent assay. Low-dose PSV infection induced lung injury and immune cell infiltration in the lung. Administration of Korean red ginseng, particularly the saponin fraction, significantly reduced the excessive activation of interstitial macrophages, NK cells, and cytotoxic T cells. Additionally, Korean red ginseng promoted long-term immune memory by increasing the population of memory B cells and cytotoxic T cells in the spleen. In the treatment groups, IgM production was enhanced upon secondary PSV infection. Korean red ginseng modulates immune responses and promotes long-term immunity against low-dose PSV infection. Our data also support the potential of Korean red ginseng as a complementary therapeutic strategy for COVID-19 and an enhancer of vaccine efficacy.

Immunosenescence is characterized by an age-associated decline in immune function, particularly involving T-cell dysfunction, which increases susceptibility to infections and chronic diseases. This study investigated the anti-aging and immunomodulatory effects of American ginseng extract (G1899) using in vitro and in vivo models of aging. Cellular senescence was induced in HepG2 cells by D-galactose treatment, followed by exposure to G1899 (20 and 100 μg/mL). Senescence-associated markers were assessed to evaluate cellular aging. An aging mouse model was established in male C57BL/6 mice through intraperitoneal administration of D-galactose (500 mg/kg) and tert-butyl hydroperoxide (0.4 mmol/kg), and G1899 was orally administered at 400 mg/kg. Thymic immune cell subsets and aging-related protein expression were analyzed using flow cytometry and Western blotting. G1899 significantly reduced p21 expression and senescence-associated β-galactosidase activity in senescent HepG2 cells. In aging-induced mice, G1899 restored CD4⁺ and CD8⁺ T-cell populations, normalized naïve T-cell levels, and reduced anergic CD28-negative T cells. Furthermore, G1899 regulated the expression of key aging-related proteins, including FOXO1, Sirt1, p53, and CD38. These findings demonstrate that G1899 attenuates age-related immune alterations by restoring thymic T-cell homeostasis and regulating aging-associated molecular pathways.

Etoposide, an anticancer drug that inhibits topoisomerase II, is commonly used in combination chemotherapy. However, the impact of O-GlcNAcylation regulation on etoposide’s anticancer effects has rarely been investigated. This study evaluated the effect of etoposide on cellular O-GlcNAcylation and whether modulating this process enhances etoposide-induced apoptosis. O-GlcNAc expression was measured after 24 h of etoposide treatment, and the effect of O-GlcNAc transferase (OGT) inhibition by OSMI-1 on etoposide’s anticancer activity in HepG2 human liver cancer cells was quantitatively analyzed. Additionally, molecular analyses were used to confirm that the observed effects were mediated by p53-induced apoptosis. Etoposide reduced O-GlcNAcylation in a dose-dependent manner without directly interacting with OGT. Cotreatment with 20 μM of OSMI-1 lowered the IC₅₀ value for cell viability by approximately 1.64-fold to 60.68 μM and increased the EC₅₀ value for cytotoxicity by around 4.07-fold to 43.41 μM. Furthermore, this synergistic effect was linked to the activation of the p53/caspase-3/PARP1 pathway. These findings suggest that downregulating O-GlcNAcylation may enhance the efficacy of etoposide-based chemotherapy and help overcome tumor resistance.