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

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-beta (TGF-beta) 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-beta and ERK1/2 signaling pathways in a UC rat model, indicating its potential antioxidant and anti-inflammatory properties.