Abstract

Abstract Background In the last years there is a great interest in the characterization of natural compounds extracted from plants or omega-3 derived molecules for their possible therapeutic effects. In this scenario, the seeds of Nigella sativa and Nigella orientalis (plants with great relevance in North African traditional medicine) have shown beneficial effects in reducing inflammation. Similarly, the addition of Maresin 2 (pro-resolving mediator) to experimental animals improved symptoms in various models of inflammation. However, there is no information on the role that these potential therapies may play in the cellular and molecular processes leading to the resolution of inflammation at the intestinal level. Methods Eight-week-old female C57Bl/6 mice (n=30) were subjected to a DSS-induced colitis model; mice received 1.8% (weight/volume) DSS in the drinking water for 6 days followed by 6 days of regular drinking water. Mice were treated from day 5 to day 12 with vehicle, Nigella Sativa, Nigella Orientalis, and Maresin-2. After that, histology studies, flow cytometry, expression analysis and migration experiments were performed. Results In all the treatment groups there was a significant reduction in weight loss and improved DAI scores compared to control group. Significant differences were also observed in the epithelial score and in the infiltration score. Analysis of the immune cell infiltrate revealed that only neutrophil numbers were downregulated after the administration of the indicated treatments. Further in vivo and in vitro studies demonstrated that Nigella Sativa and Nigella Orientalis were able to decrease neutrophil viability and migration. By contrast, Mar2 seemed to affect neutrophil infiltration through indirect mechanisms and by regulating the expression of chemotactic factors Conclusion Overall, our study reveals novel compounds able to regulate the resolution of intestinal inflammation in vivo, and this occurs, by the modulation of neutrophil presence into the colon lamina propria.

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