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

Abstract

AIMS:

To further explore the anti-inflammatory properties of d-Limonene.

MAIN METHODS:

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.

KEY FINDINGS:

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 56 days of dietary supplementation with OPE.

SIGNIFICANCE:

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.

• Authors: Patrizia A d'Alessio, Rita Ostan, Jean-François Bisson, Joerg D Schulzke, Matilde V Ursini, Marie C Béné
• Journal: Life sciences (Life Sci) Vol. 92 Issue 24-26 Pg. 1151-6 (Jul 10 2013) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 23665426 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cyclohexenes
• Terpenes
• Limonene

Topics

• Administration, Oral
• Aged
• Aged, 80 and over
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage)
• Colitis (drug therapy, pathology)
• Cyclohexenes (administration & dosage)
• Dietary Supplements
• Female
• HT29 Cells
• Humans
• Limonene
• Male
• Mice
• Rats
• Rats, Wistar
• Terpenes (administration & dosage)