D-limonene exhibits anti-inflammatory and antioxidant properties in an ulcerative colitis rat model via regulation of iNOS, COX-2, PGE2 and ERK signaling pathways

Mol Med Rep. 2017 Apr;15(4):2339-2346. doi: 10.3892/mmr.2017.6241. Epub 2017 Feb 22.


D-limonene has been demonstrated to have important immunomodulatory properties, including antitumor effects, and may alleviate asthma and allergies. In the present study, the anti‑inflammatory effects of D‑limonene were investigated in an ulcerative colitis (UC) rat model. Healthy male Sprague‑Dawley rats were randomly divided into control, untreated UC, and treatment with 50 or 100 mg/kg D‑limonene UC groups. In UC rats, disease activity and colonic mucosa damage were significantly reduced by the anti‑inflammatory effects of D‑limonene, via suppression of matrix metalloproteinase (MMP)‑2 and ‑9 gene expression. In addition, treatment with D‑limonene significantly increased antioxidant, inducible nitric oxide synthase (iNOS) and cyclooxygenase‑2 (COX‑2) protein expression levels in UC rats. A decrease in prostaglandin E2 (PGE2) production, transforming growth factor‑β (TGF‑β) gene expression and an increase phosphorylated‑extracellular signal regulated kinase (ERK) 1/2 expression levelswere observed in UC rats treated with D‑limonene. In conclusion, D‑limonene reduced MMP‑2 and ‑9 mRNA expression levels via regulation of the iNOS, COX‑2, PGE2, TGF‑β and ERK1/2 signaling pathways in a UC rat model, indicating its potential antioxidant and anti‑inflammatory properties.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / therapeutic use*
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / pathology
  • Colon / drug effects*
  • Colon / immunology
  • Colon / pathology
  • Cyclohexenes / therapeutic use*
  • Cyclooxygenase 2 / immunology
  • Dinoprostone / immunology
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Limonene
  • MAP Kinase Signaling System / drug effects
  • Male
  • Nitric Oxide Synthase Type II / immunology
  • Rats, Sprague-Dawley
  • Terpenes / therapeutic use*


  • Anti-Inflammatory Agents
  • Antioxidants
  • Cyclohexenes
  • Terpenes
  • Limonene
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Dinoprostone