In Vivo and In Vitro Study on the Efficacy of Terpinen-4-ol in Dextran Sulfate Sodium-Induced Mice Experimental Colitis

The purpose of this study was to investigate the protective effects of Terpinen-4-ol (TER) on dextran sulfate sodium (DSS)-induced experimental colitis and clarify the possible mechanisms. , an acute colitis model was used to confirm the anti-inflammatory activity and the possible mechanisms of TER in C57BL/6 and NLRP3 mice. , we performed further study, using RAW264.7 cells and Caco-2 cells, to confirm the molecular mechanisms of TER on inflammatory response. In C57BL/6 mice, TER alleviated DSS-induced disease activity index (DAI), colon length shortening, colonic pathological damage, and myeloperoxidase (MPO) activities. The production of pro-inflammatory mediators was significantly decreased by TER. Furthermore, TER inhibited NF-κB and NLRP3 inflammasome activation. Surprisingly, TER reduced the plasmatic lipopolysaccharide (LPS) concentration and re-balanced ( ) and levels. In addition, TER prevented the impairment of colon epithelium barrier by regulating the expression of zonula occludens-1 and occludin. , the results showed that TER significantly suppressed NLRP3 inflammasome activation in LPS-stimulated RAW264.7 cells, as indicated by decreased expression of NLRP3 and caspase-1, and lowered interleukin-1β secretion. In contrast, mice deficient for NLRP3 were less sensitive to DSS-induced acute colitis, and TER treatment exerted little protective effect on DSS-induced intestinal inflammation in NLRP3 mice. The protective effect of TER may be largely attributed to its inhibition of NLRP3 inflammasome activation in colon. Taken together, our findings showed that TER might be a potential agent for the treatment of ulcerative colitis.