Anti-nociceptive and anti-inflammatory effect of imperatorin: evidences for involvement of COX-2, iNOS, NF?B and inflammatory cytokines

Aim: The objective of the current investigation was to explore the analgesic effect of naturally occurring furanocoumarin, imperatorin and the involvement of inducible cyclooxygenase (COX-2), inducible nitric oxide synthase (iNOS), NF?B and cytokines in the observed effect. Materials and methods: Anti-nociceptive effect was explored by inducing chemical hyperalgesia using acetic acid and formalin in mice. ED50 of imperatorin was calculated in acetic acid model. Modulation of cyclooxygenase and nitric oxide pathway by imperatorin was examined by stimulator/precursor challenge with substance P and L-arginine, respectively and quantification of COX-2, iNOS and NF?B expression by immunohistochemical analysis in spinal tissues. Involvement of inflammatory cytokines TNF-? and IL-1? was investigated using LPS challenge and subsequent ELISA analysis of these inflammatory mediators in serum. Carrageenan inflicted paw edema was employed to explore the anti-inflammatory activity of imperatorin. Results: A significant reduction in the nociceptive behaviour was observed with imperatorin treatment in acetic acid and formalin test. ED50 of imperatorin was found to be 4.53?mg/kg. Pre-treatment with substance P and L-arginine significantly attenuated the anti-nociceptive activity of imperatorin in formalin test. Immunohistochemical findings revealed marked decrease in spinal COX-2, iNOS and NF?B expression. Imperatorin administration significantly reduced LPS induced rise in level of TNF-? and IL-1? dose dependently. In carrageenan-induced paw edema test, maximum possible anti-inflammatory effect of imperatorin was evident after 240?min of carrageenan administration. Conclusion: Current investigation revealed that anti-nociceptive and anti-inflammatory potential of imperatorin is probably mediated through the attenuation of COX-2, iNOS, NF?B activity and reduction in circulatory cytokines.