Comparison of immunoregulatory effects of polysaccharides from three natural herbs and cellular uptake in dendritic cells.

Polysaccharides from different types of natural herbs have not been compared with each other to determine their differential potencies on innate immune response, such as maturation of dendritic cells (DC). In addition, the role of endocytosis of polysaccharides in DC maturation has not been explored previously. Polysaccharides isolated from Astragalus membranaceus (APS), Ganoderma lucidum (GLP) and Radix ophiopogonis (OGP) were characterized and applied in bone marrow derived DC. Compared to immature DC, three polysaccharides with immunoactivities showed elongated dendrites, decreased phagocytic abilities, phenotypic changes (CD40/MHCII/CD80/CD86) and increased level of nitric oxide (NO) in a dose dependent manner. Interestingly, blockage of NO by iNOS inhibitor slightly decreased CD40 and MHCII but not CD80/CD86 expression induced by polysaccharides, indicating that NO was partially involved in DC maturation. In addition, GLP can enter cells in a dose and time dependent manner, shown as punctate distribution in the cytoplasm. Endocytic inhibitors sodium azide and brefeldinA that were demonstrated to inhibit cellular uptake of GLP can block phenotypic maturation of DC. Taken together, these results suggested that polysaccharides from natural herbs are effective immunostimulators with variable potencies ranking as GLP>APS>OGP, and the increase of NO level as well as the increase in polysaccharide endocytosis could be the novel strategies for improved innate response and immunotherapy.