Abstract
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. In vivo, an acute colitis model was used to confirm the anti-inflammatory activity and the possible mechanisms of TER in C57BL/6 and NLRP3−/− mice. In vitro, 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 Escherichia coli (E. coli) and Lactobacillus levels. In addition, TER prevented the impairment of colon epithelium barrier by regulating the expression of zonula occludens-1 and occludin. In vitro, 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.
Highlights
Inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis (UC), is a nonspecific, chronic, and relapsing inflammation of the gastrointestinal [1]
To investigate the protective effect of TER on UC, we established a model of dextran sulfate sodium (DSS)-induced mice colitis by feeding C57BL/6 mice with drinking water containing 2.5% DSS for 7 days
The disease activity index (DAI) scores were lower in the DSS-induced mice that received TER administration vs that in the group treated with only DSS (Figure 1B)
Summary
Inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis (UC), is a nonspecific, chronic, and relapsing inflammation of the gastrointestinal [1]. UC, an intractable IBD, is characterized by weight loss, diarrhea, rectal bleeding, and abdominal pain, which affects millions of patients worldwide and increases the risk of colon cancer [2, 3]. The etiology and pathogenesis of UC are complicated and remain uncertain, genetic susceptibility of the host, the host immune system, the intestinal microflora, and changed colonic barrier function have been found to be about the developments and course of UC [4]. NF-κB induces the production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-12 (IL-12) [5]. Emerging evidence suggests the pivotal role of NOD-like receptor family pyrin domain containing 3 (NLRP3) in the developments and pathogenesis of IBD [6]. The NLRP3 activation could lead to the maturation and secretion of highly pro-inflammatory IL-1β
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
