title: Antinociceptive and Anti-Inflammatory Effects of Zerumbone against Mono-Iodoacetate-Induced Arthritis.
abstract: The fresh rhizome of Zingiber zerumbet Smith (Zingiberaceae) is used as a food flavoring and also serves as a folk medicine as an antipyretic and for analgesics in Taiwan. Zerumbone, a monocyclic sesquiterpene was isolated from the rhizome of Z. zerumbet and is the major active compound. In this study, the anti-inflammatory and antinociceptive effects of zerumbone on arthritis were explored using in vitro and in vivo models. Results showed that zerumbone inhibited inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase (COX)-2 expressions, and NO and prostaglandin E₂ (PGE₂) production, but induced heme oxygenase (HO)-1 expression in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. When zerumbone was co-treated with an HO-1 inhibitor (tin protoporphyrin (SnPP)), the NO inhibitory effects of zerumbone were recovered. The above results suggest that zerumbone inhibited iNOS and COX-2 through induction of the HO-1 pathway. Moreover, matrix metalloproteinase (MMP)-13 and COX-2 expressions of interleukin (IL)-1β-stimulated primary rat chondrocytes were inhibited by zerumbone. In an in vivo assay, an acetic acid-induced writhing response in mice was significantly reduced by treatment with zerumbone. Furthermore, zerumbone reduced paw edema and the pain response in a mono-iodoacetate (MIA)-induced rat osteoarthritis model. Therefore, we suggest that zerumbone possesses anti-inflammatory and antinociceptive effects which indicate zerumbone could be a potential candidate for osteoarthritis treatment.
authors.affiliation: Department of Food Science, Nutrition, and Nutraceutical Biotechnology, Shih Chien University, Taipei City 10462, Taiwan. swecon@g2.usc.edu.tw.|School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei City 11031, Taiwan. swecon@g2.usc.edu.tw.
authors.forename: Ting-Yi
authors.initials: TY
authors.lastname: Chien
authors.affiliation: Division of Uro-Oncology, Department of Surgery, Chi Mei Medical Center, Tainan City 73657, Taiwan. skhsteven@yahoo.com.tw.|Department of Applied Life Science and Health, Chia Nan University of Pharmacy &amp; Science, Tainan City 71710, Taiwan. skhsteven@yahoo.com.tw.
authors.forename: Steven Kuan-Hua
authors.initials: SK
authors.lastname: Huang
authors.affiliation: Ph.D. Program for Clinical Drug Discovery of Chinese Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei City 11031, Taiwan. cjlee@tmu.edu.tw.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei City 11031, Taiwan. powei@tmu.edu.tw.
authors.forename: Po-Wei
authors.initials: PW
authors.lastname: Tsai
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei City 11031, Taiwan. crystal@tmu.edu.tw.|Orthopedics Research Center, Taipei Medical University Hospital, Taipei City 11031, Taiwan. crystal@tmu.edu.tw.
authors.forename: Ching-Chiung
authors.initials: CC
authors.lastname: Wang
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D001169:Arthritis, Experimental; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012717:Sesquiterpenes; C403304:zerumbone; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D053509:Matrix Metalloproteinase 13
keywords: Zingiber zerumbet Smith; anti-inflammatory; arthritis; heme oxygenase-1; metalloproteinase; zerumbone