title: Oral administration of d-limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans.
abstract: OBJECTIVE
  To further explore the anti-inflammatory properties of d-Limonene.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Biopark Cancer Campus, University Paris Sud-11, 94807 Villejuif, France. endocell@wanadoo.fr
authors.forename: Patrizia A
authors.initials: PA
authors.lastname: d'Alessio
authors.forename: Rita
authors.initials: R
authors.lastname: Ostan
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bisson
authors.forename: Joerg D
authors.initials: JD
authors.lastname: Schulzke
authors.forename: Matilde V
authors.initials: MV
authors.lastname: Ursini
authors.forename: Marie C
authors.initials: MC
authors.lastname: Béné
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology*; D053138:Cyclohexenes / Q000008:administration & dosage*; D019587:Dietary Supplements; D005260:Female; D019073:HT29 Cells; D006801:Humans; D000077222:Limonene; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000008:administration & dosage*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053138:Cyclohexenes; D013729:Terpenes; D000077222:Limonene