Oral administration of d-Limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans |
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Authors: | Patrizia A d'Alessio Rita Ostan Jean-François Bisson Joerg D Schulzke Matilde V Ursini Marie C Béné |
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Institution: | 1. Biopark Cancer Campus, University Paris Sud-11, 94807 Villejuif, France;2. Department of Experimental, Diagnostic and Specialty Medicine - University of Bologna, 40126 Bologna, Italy;3. ETAP Research Centre, 54500 Vand?uvre-lès-Nancy, France;4. Department of General Medicine and Gastroenterology, Charité, Campus Benjamin Franklin, Berlin, Germany;5. Institute of Genetics and Biophysics, A. Buzzati-Traverso, CNR, Naples, Italy;6. Hematology Laboratory, CHU de Nantes, Nantes, France |
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Abstract: | AimsTo further explore the anti-inflammatory properties of d-Limonene.Main methodsA rat model was used to compare evolution of TNBS (2,5,6-trinitrobenzene sulfonic acid)-induced colitis after oral feeding with d-Limonene compared to ibuprofen. Peripheral levels of TNF-α (Tumor Necrosis Factor alpha) were assessed in all animals. Cell cultures of fibroblasts and enterocytes were used to test the effect of d-Limonene respectively on TNFα-induced NF-κB (nuclear factor-kappa B) translocation and epithelial resistance. Finally, plasmatic inflammatory markers were examined in an observational study of diet supplementation with d-Limonene-containing orange peel extract (OPE) in humans.Key findingsAdministered per os at a dose of 10 mg/kg p.o., d-Limonene induced a significant reduction of intestinal inflammatory scores, comparable to that induced by ibuprofen. Moreover, d-Limonene-fed rats had significantly lowered serum concentrations of TNF-α compared to untreated TNBS-colitis rats. The anti-inflammatory effect of d-Limonene also involved inhibition of TNFα-induced NF-κB translocation in fibroblast cultures. The application of d-Limonene on colonic HT-29/B6 cell monolayers increased epithelial resistance. Finally, inflammatory markers, especially peripheral IL-6, markedly decreased upon OPE supplementation of elderly healthy subjects submitted or not to 56 days of dietary supplementation with OPE.SignificanceIn conclusion, d-Limonene indeed demonstrates significant anti-inflammatory effects both in vivo and in vitro. Protective effects on the epithelial barrier and decreased cytokines are involved, suggesting a beneficial role of d-Limonene as diet supplement in reducing inflammation. |
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