The ameliorative effect of hyaluronic acid-astaxanthin nanoparticles on colitis through reducing oxidative stress, enhancing colon barrier, and reshaping intestinal microbiota.

Astaxanthin (AST) is recognize as the most potent antioxidant found in nature; however, its practical applications have been limited due to its structural instability. In this study, hyaluronic acid (HA) was used to stabilize AST, and they were both covalently linked via ethylenediamine to synthesis the hyaluronic acid-astaxanthin complex, which was subsequently formulated into hyaluronic acid-astaxanthin nanoparticles (HA-ASTNPs) in PBS. HA-ASTNPs was spherical with a particle size of 172.6 ± 2.1 nm and a zeta potential of -16.6 ± 0.8 mV. The encapsulation efficiency and loading capacity of AST in HA-ASTNPs were 72.7 % and 44.8 %, respectively. HA-ASTNPs exhibited a sustained release of AST slowly in simulated gastric and intestinal fluid, while a rapid release was observed in simulated colon fluid. In DSS-induced colitis mice, HA-ASTNPs relieved colon inflammation by inhibiting the NLRP3 pathway. Further analysis revealed the nanoparticles alleviated oxidative stress in colon tissues via activating the Nrf2/HO-1 pathway and restore colon barrier by promoting the expression of ZO-1, Occludin, and MUC2. Moreover, HA-ASTNPs reshaped intestinal microbiota by elevating the ratio of Firmicutes/Bacteroidota, increasing the abundance of Paraclostridium, Paeniclostridium, and [Eubacterium]_fissicatena_group, and reducing the population of Comamonas, Dysgonomonas, Sporomusa, and Slistipes. In sum, HA-ASTNPs ameliorated UC involving in oxidative stress, inflammatory reaction, colon barrier, and intestinal microbiota. HA-ASTNPs had the potential to prevent or treat DSS-induced ulcerative colitis.