Oral administration of d-Limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans

• Published in: Life sciences (1973) Vol. 92; no. 24-26; pp. 1151 - 1156
• Main Authors: d'Alessio, Patrizia A., Ostan, Rita, Bisson, Jean-François, Schulzke, Joerg D., Ursini, Matilde V., Béné, Marie C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 10.07.2013
• Subjects: Administration, Oral; Aged; Aged, 80 and over; animal models; Animals; anti-inflammatory activity; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; blood serum; cell culture; colitis; Colitis - drug therapy; Colitis - pathology; Cyclohexenes - administration & dosage; diet study techniques; Dietary Supplements; elderly; enterocytes; Female; fibroblasts; HT29 Cells; Humans; ibuprofen; inflammation; interleukin-6; Male; Mice; NF-κB; observational studies; oral administration; Orange peel extract (OPE); orange peels; protective effect; Rats; Rats, Wistar; sulfonic acid; sulfonic acids; Terpenes - administration & dosage; TNF-α; transcription factor NF-kappa B; tumor necrosis factor-alpha; TNF-α; NF-κB; Orange peel extract (OPE)
• ISSN: 0024-3205; 1879-0631; 1879-0631
• DOI: 10.1016/j.lfs.2013.04.013

To further explore the anti-inflammatory properties of d-Limonene. A 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. Administered per os at a dose of 10mg/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 56days of dietary supplementation with OPE. In 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.