Anti-nociceptive and anti-inflammatory effect of imperatorin: evidences for involvement of COX-2, iNOS, NFκB 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), NFκB 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 NFκB expression by immunohistochemical analysis in spinal tissues. Involvement of inflammatory cytokines TNF-α and IL-1β 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 NFκB expression. Imperatorin administration significantly reduced LPS induced rise in level of TNF-α and IL-1β 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, NFκB activity and reduction in circulatory cytokines.