Specific Inulin in Codonopsis pilosula 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 Codonopsis pilosula was found to exhibit immunological enhancement both in vitro and in vivo. However, the commercial inulin, which has an almost identical molecular weight and monosaccharide composition as CPS0.2B, exhibited almost no biological activity in vitro. 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, in vivo 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.