Praeruptorin A alleviates DSS-induced acute ulcerative colitis in mice via the STAT-1/-3 pathway.

Ulcerative colitis (UC) is a serious inflammatory bowel disease with a significantly increasing incidence globally. Current treatment options often exhibit unstable efficacy and notable side effects, making the exploration of alternative therapies particularly important. Peucedanum praeruptorum Dunn, a traditional Chinese medicine, contains various bioactive compounds, among which praeruptorin A (PA) has garnered attention for its anti-inflammatory potential. This study aimed to investigate the anti-UC effects of PA in a dextran sulfate sodium (DSS)-induced colitis mouse model and in Caco-2 cells and its underlying mechanisms. Preliminary results indicate that PA alleviates symptoms of DSS-induced ulcerative colitis, significantly reduces the expression of inflammatory factors, decreases colonic apoptosis, and repairs damaged intestinal barrier function in mice. PA also had protective effects on DSS-induced barrier dysfunction and inflammation in Caco-2 cells. Further research demonstrated that PA inhibits the phosphorylation of the STAT-1 and STAT-3 proteins, whereas AG490, an inhibitor of STAT-1 and STAT-3, effectively mimics the intestinal protective effects of PA. In addition, network pharmacology and molecular docking analyses were conducted to further elucidate the molecular targets and mechanisms of PA. These analyses revealed key pathways and potential interactions, supporting the hypothesis that PA exerts its protective effects through the modulation of inflammatory and apoptotic pathways. In summary, these findings support the protective role of PA in ulcerative colitis in vivo and in vitro and suggest its potential as an intervention for the prevention and treatment of this condition.NEW & NOTEWORTHY This study revealed that praeruptorin A (PA) alleviates symptoms of ulcerative colitis in a DSS-induced mouse model, reduces inflammatory factors levels, and promotes intestinal barrier repair in both DSS-induced colitis model mice and Caco-2 cells. The effects of PA are linked to STAT-1 and STAT-3 inhibition, highlighting its potential as a therapeutic intervention.