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

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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 E ₂ (PGE ₂) 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.

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Matrix metalloproteinases: role in arthritis.

Peter S Burrage, Kimberlee S Mix, Constance Brinckerhoff (2006)

The irreversible destruction of the cartilage, tendon, and bone that comprise synovial joints is the hallmark of both rheumatoid arthritis (RA) and osteoarthritis (OA). While cartilage is made up of proteoglycans and type II collagen, tendon and bone are composed primarily of type I collagen. RA is an autoimmune disease afflicting numerous joints throughout the body; in contrast, OA develops in a small number of joints, usually resulting from chronic overuse or injury. In both diseases, inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) stimulate the production of matrix metalloproteinases (MMPs), enzymes that can degrade all components of the extracellular matrix. The collagenases, MMP-1 and MMP-13, have predominant roles in RA and OA because they are rate limiting in the process of collagen degradation. MMP-1 is produced primarily by the synovial cells that line the joints, and MMP-13 is a product of the chondrocytes that reside in the cartilage. In addition to collagen, MMP-13 also degrades the proteoglycan molecule, aggrecan, giving it a dual role in matrix destruction. Expression of other MMPs such as MMP-2, MMP-3 and MMP-9, is also elevated in arthritis and these enzymes degrade non-collagen matrix components of the joints. Significant effort has been expended in attempts to design effective inhibitors of MMP activity and/or synthesis with the goal of curbing connective tissues destruction within the joints. To date, however, no effective clinical inhibitors exist. Increasing our knowledge of the crystal structures of these enzymes and of the signal transduction pathways and molecular mechanisms that control MMP gene expression may provide new opportunities for the development of therapeutics to prevent the joint destruction seen in arthritis.

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Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis.

S.E Bove, S.L Calcaterra, R.M Brooker … (2003)

To describe an in vivo model in the rat in which change in weight distribution is used as a measure of disease progression and efficacy of acetaminophen and two nonsteroidal anti-inflammatory drugs (NSAIDs) in a model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). Intra-articular injections of MIA and saline were administered to male Wistar rats (175-200 g) into the right and left knee joints, respectively. Changes in hind paw weight distribution between the right (osteoarthritic) and left (contralateral control) limbs were utilized as an index of joint discomfort. Acetaminophen and two archetypal, orally administered NSAIDs, naproxen and rofecoxib, were examined for their ability to decrease MIA-induced change in weight distribution. A concentration-dependent increase in change in hind paw weight distribution was noted after intra-articular injection of MIA. Both naproxen and rofecoxib demonstrated the capacity to significantly (P<0.05) decrease hind paw weight distribution in a dose-dependent fashion, indicating that the change in weight distribution associated with MIA injection is susceptible to pharmacological intervention. The determination of differences in hind paw weight distribution in the rat MIA model of OA is a technically straightforward, reproducible method that is predictive of the effects of anti-inflammatory and analgesic agents. This system may be useful for the discovery of novel pharmacologic agents in human OA.

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Pain related behaviour in two models of osteoarthritis in the rat knee.

Stuart Bevan, John Rediske, Clive Gentry … (2004)

Osteoarthritis (OA) is a major healthcare burden, with increasing incidence. Pain is the predominant clinical feature, yet therapy is ineffective for many patients. While there are considerable insights into the mechanisms underlying tissue remodelling, there is poor understanding of the link between disease pathology and pain. This is in part owing to the lack of animal models that combine both osteoarthritic tissue remodelling and pain. Here, we provide an analysis of pain related behaviours in two models of OA in the rat: partial medial meniscectomy and iodoacetate injection. Histological studies demonstrated that in both models, progressive osteoarthritic joint pathology developed over the course of the next 28 days. In the ipsilateral hind limb in both models, changes in the percentage bodyweight borne were small, whereas marked mechanical hyperalgesia and tactile allodynia were seen. The responses in the iodoacetate treated animals were generally more robust, and these animals were tested for pharmacological reversal of pain related behaviour. Morphine was able to attenuate hyperalgesia 3, 14 and 28 days after OA induction, and reversed allodynia at days 14 and 28, providing evidence that this behaviour was pain related. Diclofenac and paracetamol were effective 3 days after arthritic induction only, coinciding with a measurable swelling of the knee. Gabapentin varied in its ability to reverse both hyperalgesia and allodynia. The iodoacetate model provides a basis for studies on the mechanisms of pain in OA, and for development of novel therapeutic analgesics.

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Author and article information

Contributors

Paula Andrade: Role: Academic Editor

Patrícia Valentão: Role: Academic Editor

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 18 February 2016

Publication date Collection: February 2016

Volume: 17

Issue: 2

Electronic Location Identifier: 249

Affiliations

[1 ]Department of Food Science, Nutrition, and Nutraceutical Biotechnology, Shih Chien University, Taipei City 10462, Taiwan; swecon@ 123456g2.usc.edu.tw

[2 ]School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei City 11031, Taiwan; powei@ 123456tmu.edu.tw

[3 ]Division of Uro-Oncology, Department of Surgery, Chi Mei Medical Center, Tainan City 73657, Taiwan; skhsteven@ 123456yahoo.com.tw

[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; cjlee@ 123456tmu.edu.tw

[6 ]Orthopedics Research Center, Taipei Medical University Hospital, Taipei City 11031, Taiwan

Author notes

[* ]Correspondence: crystal@ 123456tmu.edu.tw ; Tel.: +886-2-2736-1661 (ext. 6161)

[†]

These authors contributed equally to this work.

Article

Publisher ID: ijms-17-00249

DOI: 10.3390/ijms17020249

PMC ID: 4783979

PubMed ID: 26901193

SO-VID: 0a0f63c1-a66a-4d15-97b3-acd3b692c860

License:

This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

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

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Abstract

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Biomarkers for Inflammatory Lung Disease

Most cited references 26

Matrix metalloproteinases: role in arthritis.

Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis.

Pain related behaviour in two models of osteoarthritis in the rat knee.

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