Anti-cancer activity of Angelica gigas by increasing immune response and stimulating natural killer and natural killer T cells.

BACKGROUND: The polysaccharide component of Angelica gigas induces immuno-stimulatory effects on innate immune cells. However, it is unclear whether A. gigas' adjuvant activity on the immune system can elicit anti-cancer responses. METHODS: A water-soluble immuno-stimulatory component of A. gigas was prepared. How this ISAg modulated the activation of innate immune cells such as dendritic cells (DCs) was examined. ISAg-induced cytotoxic activity via natural killer (NK) and NKT cells was also tested using a tumor-bearing mouse model. RESULTS: ISAg treatment induced nitric oxide (NO) production and cytokine gene expression involved in innate immune responses. ISAg activated macrophages and DCs to secrete cytokine IL-12, through the TLR4 signaling pathway. IL-12 plays a crucial role in ISAg-mediated NK and NKT cell activation. Thus, the anti-cancer activity of NK and NKT cells induced ISAg-mediated cytotoxicity of B16 melanoma cells in mice. CONCLUSIONS: These results indicated that the natural ingredient, ISAg, has adjuvant activity to induce strong anti-cancer activity of NK and NKT cells in vivo.

Fisetin-Rich Extracts of Rhus verniciflua Stokes Improve Blood Flow Rates in Mice Fed Both Normal and High-Fat Diets.

Although it has been previously reported that Rhus verniciflua Stokes (RVS) possesses in vitro anti-inflammatory activity, the precise in vivo mechanisms of RVS extracts and a main active component called fisetin have not been well elucidated. In this study, using newly developed protocols, we prepared urushiol-free but fisetin-enriched RVS extracts and investigated their effects on the vascular immune system. We found that the water-soluble fractions of detoxified RVS with the flavonoid fisetin can inhibit lipopolysaccharide-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2). Furthermore, RVS can reduce inducible nitric oxide synthase and COX2 gene expression levels, which are responsible for NO and PGE2 production, respectively, in RAW264.7 macrophage cells. Because inflammation is linked to the activation of the coagulation system, we hypothesized that RVS and its active component fisetin possess anticoagulatory activities. As expected, we found that both RVS and fisetin could inhibit the coagulation of human peripheral blood cells. Moreover, in vivo RVS treatment could return the retarded blood flow elicited by a high-fat diet (HFD) back to the normal level in mice. In addition, RVS treatment has significantly reduced body weight gained by HFD in mice. Taken together, the fisetin-rich RVS extracts have potential antiplatelet and antiobesity activities and could be used as a functional food ingredient to improve blood circulation.