Antiviral activity of 20(R)-ginsenoside Rh2 against murine gammaherpesvirus.

BACKGROUND: Ginsenosides are the major components of Panax ginseng Meyer, an herbal medicine used for the treatment of various diseases. Different ginsenosides contribute to the biological properties of ginseng, such as antimicrobial, anticancer, and immunomodulatory properties. In this study, we investigated the antiviral effects of 15 ginsenosides and compound K on gammaherpesvirus. METHODS: The antiviral activity of ginsenosides was examined using the plaque-forming assay and by analyzing the expression of the lytic gene. RESULTS: 20(R)-Ginsenoside Rh2 inhibited the replication and proliferation of murine gammaherpesvirus 68 (MHV-68), and its half-maximal inhibitory concentration (IC50) against MHV-68 was estimated to be 2.77 µM. In addition, 20(R)-ginsenoside Rh2 inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lytic replication of human gammaherpesvirus in the Kaposi's sarcoma-associated herpesvirus (KSHV)-positive cell line BC3. CONCLUSION: Our results indicate that 20(R)-ginsenoside Rh2 can inhibit the replication of mouse and human gammaherpesviruses, and thus, has the potential to treat gammaherpesvirus infection.

Identification of aminosulfonylarylisoxazole as microRNA-31 regulators.

The discovery of small-molecule regulators of microRNAs remains challenging, but a few have been reported. Herein, we describe small-molecule inhibitors of miR-31, a tumor-associated microRNA (miRNA), identified by high-throughput screening using a cell-based reporter assay. Aminosulfonylarylisoxazole compounds exhibited higher specificity for miR-31 than for six other miRNAs, i.e., miR-15a, miR-16, miR-21, miR-92a-1, miR-146a, and miR-155, and increased the expression of miR-31 target genes. The down-regulation of mature miR-31 was observed, while its precursor form increased following treatment with the compounds. Thus, the compounds may target the processing of pre-miR-31 into mature miR-31 and thereby inhibit the production of mature miR-31.

T Cell Stimulatory Effects of Korean Red Ginseng through Modulation of Myeloid-Derived Suppressor Cells.

Myeloid-derived suppressor cells (MDSCs) actively suppress immune cells and have been considered as an impediment to successful cancer immunotherapy. Many approaches have been made to overcome such immunosuppressive factors and to exert effective anti-tumor effects, but the possibility of using medicinal plants for this purpose has been overlooked. Korean red ginseng (KRG) is widely known to possess a variety of pharmacological properties, including immunoboosting and anti-tumor activities. However, little has been done to assess the anti-tumor activity of KRG on MDSCs. Therefore, we examined the effects of KRG on MDSCs in tumor-bearing mice and evaluated immunostimulatory and anti-tumor activities of KRG through MDSC modulation. The data show that intraperitoneal administration of KRG compromises MDSC function and induces T cell proliferation and the secretion of IL-2 and IFN-γ, while it does not exhibit direct cytotoxicity on tumor cells and reduced MDSC accumulation. MDSCs isolated from KRG-treated mice also express significantly lower levels of inducible nitric oxide synthase and IL-10 accompanied by a decrease in nitric oxide production compared with control. Taken together, the present study demonstrates that KRG enhances T cell function by inhibiting the immunosuppressive activity of MDSCs and suggests that although KRG alone does not exhibit direct anti-tumor effects, the use of KRG together with conventional chemo- or immunotherapy may provide better outcomes to cancer patients through MDSC modulation.