title: 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.
authors.affiliation: BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Park
authors.affiliation: BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Hye Ja
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Jin Kyu
authors.initials: JK
authors.lastname: Choi
authors.affiliation: BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Hyun Ji
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: June Hee
authors.initials: JH
authors.lastname: Kang
authors.affiliation: BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: You Ri
authors.initials: YR
authors.lastname: Kim
authors.affiliation: National Cancer Center, Goyang 449-729, Republic of Korea.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Kang
authors.affiliation: College of Pharmacy, CHA University, Seongnam-si, Gyeonggi-do 463-836, Republic of Korea.
authors.forename: Jung Ki
authors.initials: JK
authors.lastname: Yoo
authors.affiliation: Korea Pharmacology Research Center, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 305-343, Republic of Korea.
authors.forename: Hee Yeong
authors.initials: HY
authors.lastname: Cho
authors.affiliation: College of Pharmacy, CHA University, Seongnam-si, Gyeonggi-do 463-836, Republic of Korea.
authors.forename: Jin Kyeoung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Graduate School of Medicine, Dongguk University Ilsan Hospital, Republic of Korea.
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Kim
authors.affiliation: BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Jong Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea. Electronic address: uatheone@dongguk.edu.
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Lee
mesh_terms: D032429:Alpinia; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D016227:Benzoquinones / Q000633:toxicity; D002351:Carrageenan / Q000633:toxicity; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D055670:Medicine, Korean Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000188:drug therapy; D010946:Plants, Medicinal; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000700:Analgesics; D016227:Benzoquinones; D047188:Chalcones; D052246:Cyclooxygenase 2 Inhibitors; D034741:RNA, Small Interfering; C000717609:Tgm2 protein, rat; C029322:phenylbenzoquinone; D002351:Carrageenan; D051546:Cyclooxygenase 2; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; C436747:cardamonin
keywords: Alpinia katsumadai; Anti-nociceptive; Cardamonin; Carrageenan-induced hyperalgesia; Phenylbenzoquinone; Transglutaminase-2