Novel anti-nociceptive effects of cardamonin via blocking expression of cyclooxygenase-2 and transglutaminase-2

Abstract

Recently, we reported that Alpinia katsumadai (AK) has anti-nociceptive activity in vivo and that cardamonin (CON) from AK suppresses the activity and expression of transglutaminase-2 (Tgase-2). However, it remains unknown whether CDN contributes to the anti-nociceptive activities of AK in vivo. We examined the anti-inflammatory effects of CDN in MG63 osteoblast-like cells and Raw264.7 macrophage-like cells treated with interleukin-1 beta treatment. CON suppressed the expression of Tgase-2, cyclooxygenase-2 (COX-2), and p65 (nuclear factor-kappa B) in a concentration-dependent manner, and restored the expression of I kappa B in MG63 and Raw264.7 cells. However, CON did not inhibit the activity of COX-2. Gene silencing of Tgase-2 reduced the COX-2 expression in MG63 cells. Phenylbenzoquinone (PBQ)-induced writhing, carrageenan-induced hyperalgesia, and rota-rod test were used to evaluate the anti-nociceptive activity in vivo. CDN (3-30 mg/kg, orally administered) significantly inhibited PBQ-induced writhing. CON also produced a significant, dose-dependent increase in the withdrawal response latencies in carrageenan-induced hyperalgesia. The effects of CON on PBQ-induced writhing were not caused by impaired motor functions. These results suggest that CON might be helpful in controlling the pain from inflammatory diseases. (C) 2013 Elsevier Inc. All rights reserved.