10-hydroxy-2-decenoic acid ameliorates liver injury secondary to DSS-induced colitis by regulating TLR9-NLRP1/NLRP3-medicated pyroptosis

Liver injury is a common complication associated with colitis. 10-hydroxy-2-decenoic acid (10-HDA), a bioactive component found in royal jelly, is recognized for its significant anti-inflammatory properties. In this study, a colitis-associated liver injury model was induced in C57BL/6 mice by administering 2.5 % dextran sulfate sodium (DSS) for 7 days. Mice were randomly assigned to control, DSS, and DSS + 10-HDA groups. The bioavailability of 10-HDA was confirmed through mass spectrometry analysis. Our results indicate that 10-HDA significantly mitigated DSS-induced hepatic injury, as evidenced by reduced histopathological scores, decreased liver enzyme levels, and lower concentrations of inflammatory cytokines. Furthermore, 10-HDA effectively downregulated the expression of TLR9 and alleviated the activation of pyroptosis-associated proteins, including NLRP3, NLRP1, ASC, and N-GSDMD. Overall, 10-HDA ameliorates DSS-induced liver injury in the ulcerative colitis (UC) model by modulating NLRP1/NLRP3-mediated pyroptosis and regulating the immune response, highlighting the therapeutic potential of 10-HDA in managing hepatic complications associated with UC. • 10-HDA alleviates DSS-induced hepatic injury, indicating therapeutic potential for inflammatory bowel disease-associated hepatopathy. • 10-HDA regulates TLR9 expression and downregulates pyroptosis-associated proteins, highlighting its dual regulatory mechanism in inflammatory signaling and pyroptotic pathways.