Specific Inulin in <i>Codonopsis pilosula</i> Exerts Immunological Enhancement by Promoting Cellular Uptake and Regulating p65-Dependent MAPK and NF-κb Pathways

An inulin-type fructan (CPS0.2B) from an edible traditional Chinese medicine (TCM) named <i>Codonopsis pilosula</i> was found to exhibit immunological enhancement both <i>in vitro</i> and <i>in vivo</i>. However, the commercial inulin, which has an almost identical molecular weight and monosaccharide composition as CPS0.2B, exhibited almost no biological activity <i>in vitro.</i> We found that this difference was attributed to the smaller particle size of CPS0.2B, facilitating enhanced cellular uptake through endocytosis. Further investigation into the corresponding immune-enhancing effect using THP-1 macrophage cells indicated that CPS0.2B can effectively activate the MAPK and NF-κB signaling pathways by stimulating the p65 protein both inside and outside the cell membrane. Additionally, <i>in vivo</i> strudy further confirmed CPS0.2B had an immune-enhancing effect on CTX-induced immune suppression model in mice. This study confirmed the immune-enhancing activity and related mechanisms of the inulin-type fructan CPS0.2B and, more importantly, demonstrated the significant role of the advanced structure of the polysaccharides in immunomodulatory effects.