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.
Rheumatoid arthritis (RA) is a chronic immune disease characterized by the infiltration of immune cells and the proliferation of fibroblast-like synoviocytes (FLS) at the joint site, leading to inflammation and joint destruction. However, the available treatment options targeting both inflammatory and proliferative FLS are limited. Herein, this work presents three covalent organic frameworks (COFs) photothermal composite systems modified with multi-armed polyethylene glycols (PEG) for the treatment of RA. These systems exhibit a dual response under low pH and high reactive oxygen species (ROS) conditions at the site of inflammation, with a specific focus on delivering the protein drug ribonuclease A (RNase A). Notably, molecular docking studies reveal the interaction between RNase A and NF-κB p65 protein, and Western blotting confirm its inhibitory effect on NF-κB activity. In vitro and in vivo experiments verify the significant reduction in joint swelling and deformities in adjuvant-induced arthritis (AIA) rats after treatment with RNase A delivered by multi-armed PEG-modified COF ligands, restoring joint morphology to normal. These findings underscore the promising therapeutic potential of COFs for the treatment of RA, highlighting their unique capabilities in addressing both inflammatory and proliferative aspects of the disease and expanding the scope of biomedical applications for COFs.
危险品化学品经营许可证（带存储）