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Int. J. Mol. Sci. 2016, 17(2), 249; doi:10.3390/ijms17020249

Antinociceptive and Anti-Inflammatory Effects of Zerumbone against Mono-Iodoacetate-Induced Arthritis

1
Department of Food Science, Nutrition, and Nutraceutical Biotechnology, Shih Chien University, Taipei City 10462, Taiwan
2
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei City 11031, Taiwan
3
Division of Uro-Oncology, Department of Surgery, Chi Mei Medical Center, Tainan City 73657, Taiwan
4
Department of Applied Life Science and Health, Chia Nan University of Pharmacy & Science, Tainan City 71710, Taiwan
5
Ph.D. Program for Clinical Drug Discovery of Chinese Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei City 11031, Taiwan
6
Orthopedics Research Center, Taipei Medical University Hospital, Taipei City 11031, Taiwan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editors: Paula Andrade and Patrícia Valentão
Received: 25 December 2015 / Revised: 5 February 2016 / Accepted: 6 February 2016 / Published: 18 February 2016
(This article belongs to the Special Issue Phenolics and Polyphenolics 2015)
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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. View Full-Text
Keywords: Zingiber zerumbet Smith; zerumbone; arthritis; anti-inflammatory; heme oxygenase-1; metalloproteinase Zingiber zerumbet Smith; zerumbone; arthritis; anti-inflammatory; heme oxygenase-1; metalloproteinase
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MDPI and ACS Style

Chien, T.-Y.; Huang, S.K.-H.; Lee, C.-J.; Tsai, P.-W.; Wang, C.-C. Antinociceptive and Anti-Inflammatory Effects of Zerumbone against Mono-Iodoacetate-Induced Arthritis. Int. J. Mol. Sci. 2016, 17, 249.

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