Trans-10-Hydroxy-2-Decenoic Acid Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice via Regulating the Inflammasome-Mediated Pyroptotic Pathway and Enhancing Colonic Barrier Function.

Abstract

The objective of this study is to explore the effects of 10-hydroxy-2-decenoic acid (10-HDA), the major fatty acid in royal jelly, on dextran sodium sulfate (DSS)-induced mice ulcerative colitis (UC) and its potential mechanism of action. Forty male C57BL/6 mice are randomly divided into five experimental groups: control, DSS, DSS + 25 (or 100)mgkg-1 d-1 10-HDA, and DSS + 200mgkg-1 d-1 mesalazine (ME). UC is induced in mice using 2.5% DSS in drinking water for 7 days. During the induction, these UC mice are orally administrated 10-HDA or ME per day.Meanwhile, lipopolysaccharide (LPS)/adenosine-triphosphate (ATP)-stimulated THP1 cells are used as a model to test the effects of 10-HDA. 10-HDA reduces DSS-induced pathological damage, reactive oxygen species (ROS) accumulation, neutrophil infiltration, and cytokine production in colonic tissue. Compared with the DSS group, the expressions of thioredoxin interacting protein (TXNIP), NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1), gasdermin-D (GSDMD), N-terminal domain of gasdermin-D (N-GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in the colon are decreased after administration of 10-HDA. 10-HDA also elevates the barrier integrity and the expressions of zonula occludens-1 (ZO-1) and Occludin in colonic epithelium exposed to DSS. In THP1 cells, the inflammasome-mediated pyroptosis induced by LPS/ATP is inhibited by 10-HDA pretreatment. 10-HDA alleviates DSS-induced colitis by regulating the NLRP3 inflammasome-mediated pyroptotic pathway and enhancing colonic barrier function.