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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 (CDN) 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-1β treatment. CDN suppressed the expression of Tgase-2, cyclooxygenase-2 (COX-2), and p65 (nuclear factor-κB) in a concentration-dependent manner, and restored the expression of IκB in MG63 and Raw264.7 cells. However, CDN 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. CDN also produced a significant, dose-dependent increase in the withdrawal response latencies in carrageenan-induced hyperalgesia. The effects of CDN on PBQ-induced writhing were not caused by impaired motor functions. These results suggest that CDN might be helpful in controlling the pain from inflammatory diseases.
AuthorsMi Kyung Park, Hye Ja Lee, Jin Kyu Choi, Hyun Ji Kim, June Hee Kang, Eun Ji Lee, You Ri Kim, Ju Hee Kang, Jung Ki Yoo, Hee Yeong Cho, Jin Kyeoung Kim, Chang-Hyun Kim, Jong Hwan Park, Chang Hoon Lee
JournalPharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 118 Pg. 10-5 (Mar 2014) ISSN: 1873-5177 [Electronic] United States
PMID24398147 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Analgesics
  • Benzoquinones
  • Chalcones
  • Cyclooxygenase 2 Inhibitors
  • RNA, Small Interfering
  • Tgm2 protein, rat
  • phenylbenzoquinone
  • Carrageenan
  • Cyclooxygenase 2
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins
  • cardamonin
Topics
  • Alpinia
  • Analgesics (pharmacology)
  • Animals
  • Benzoquinones (toxicity)
  • Carrageenan (toxicity)
  • Cell Line
  • Chalcones (pharmacology)
  • Cyclooxygenase 2 (genetics)
  • Cyclooxygenase 2 Inhibitors (pharmacology)
  • GTP-Binding Proteins (antagonists & inhibitors, genetics)
  • Gene Expression (drug effects)
  • Humans
  • Male
  • Medicine, Korean Traditional
  • Mice
  • Mice, Inbred ICR
  • Pain (drug therapy)
  • Plants, Medicinal
  • Protein Glutamine gamma Glutamyltransferase 2
  • RNA, Small Interfering (genetics)
  • Rats
  • Rats, Sprague-Dawley
  • Transglutaminases (antagonists & inhibitors, genetics)

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