Curcumin-chitosan microspheres inhibit epithelial cell PANoptosis: analysis of key PANoptosis gene distribution via single-cell RNA sequencing and in vivo validation in ulcerative colitis mice.

Our previous research has confirmed that curcumin ameliorates pathology of ulcerative colitis (UC) in mice. PANoptosis is closely associated with UC; however, whether curcumin-chitosan microspheres (CCM) alleviate UC by modulating intestinal epithelial cell PANoptosis remains unreported. Here, CCM significantly inhibited UC-induced damage to colon tissue, as evidenced by increased colon length and reduced DAI score, as well as lower concentrations of inflammatory factors (IL-18 and IL-1β). CCM also suppressed expression of tight junction marker ZO-1 and PANoptosis marker NLRP12 induced by UC in colon tissue, and we observed the co-localization of ZO-1 and NLRP12. scRNA-seq revealed eight subpopulations of intestinal epithelial cells and crypt top colonocytes had the highest PANoptosis score. Expression of PANoptosis-related markers (ASC, NLRP3, NLRP12, and caspase-8) was downregulated after CCM treatment in scRNA-seq data. Different concentrations of CCM (20, 40, 80 μM) did not alter the cell viability of Caco-2 cells, but significantly reduced LPS-induced death and the elevation of inflammatory factors. LPS provoked protein expression of PANoptosis-related markers in Caco-2 cells, but this effect was reversed by CCM. In conclusion, CCM ameliorate UC by inhibiting epithelial cell PANoptosis, indicating that CCM is a promising therapeutic strategy against UC from the prospective of epithelial cell PANoptosis.