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DOI: 10.1055/s-0042-113387
Suppression of Cartilage Degradation by Zingerone Involving the p38 and JNK MAPK Signaling Pathway
Publication History
received 07 March 2016
revised 04 July 2016
accepted 17 July 2016
Publication Date:
30 August 2016 (online)
Abstract
Zingerone, an active compound that is present in cooked ginger, has been claimed to be a bioactive ingredient that holds the potential of preventing and/or treating diseases involving inflammation. In this study, zingerone was used to discover its properties against joint inflammation using interleukin-1β-induced osteoarthritis in cartilage explant and cell culture models. Zingerone was supplemented into the cartilage explant and cell culture media at different concentrations along with the presence of interleukin-1β, an inducer of osteoarthritis. Markers indicating cartilage degradation, inflammation, and the signaling molecules involved in the inflammatory induction were investigated. Diacerien, an anti-osteoarthritic drug, was used as a positive control. Zingerone at a concentration of 40 µM reduced the level of matrix metalloproteinase-13 to about 31.95 ± 4.33 % compared with the interleukin-1β-treated group and halted cartilage explant degradation as indicated by reducing the accumulative release of sulfated glycosaminoglycans by falling to the control concomitantly with an elevation of the remaining contents of uronic acid and collagen in the explant tissues when zingerone was added. In the SW1353 cell line model, zingerone efficiently suppressed the expression of TNF-α, interleukin-6, and interleukin-8 mRNA levels and tended to reduce the levels of both p38 and c-Jun N-terminal kinase phosphorylation. From the results of this study, it can be concluded that zingerone potentially reduced cartilage degradation, which is partially involved in p38 and c-Jun N-terminal kinases of the mitogen activator protein kinase signaling pathway leading to the reduction of proinflammatory cytokine amplification effects and cartilage-degrading enzyme syntheses. This finding supports the contention that ginger holds positive pharmaceutical effects against osteoarthritis.
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References
- 1 Blagojevic M, Jinks C, Jeffery A, Jordan KP. Risk factors for onset of osteoarthritis of the knee in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage 2010; 18: 24-33
- 2 Goldring M. Osteoarthritis and cartilage: the role of cytokines. Curr Rheumatol Rep 2000; 2: 459-465
- 3 Caron JP, Fernandes JC, Martel-Pelletier J, Tardif G, Mineau F, Geng C, Pelletier J. Chondroprotective effect of intraarticular injections of interleukin-1 receptor antagonist in experimental osteoarthritis. Suppression of collagenase-1 expression. Arthritis Rheum 1996; 39: 1535-1544
- 4 Li NG, Shi ZH, Tang YP, Wang ZJ, Song SL, Qian LH, Qian DW, Duan JA. New hope for the treatment of osteoarthritis through selective inhibition of MMP-13. Curr Med Chem 2011; 18: 977-1001
- 5 Phitak T, Choocheep K, Pothacharoen P, Pompimon W, Premanode B, Kongtawelert P. The effects of p-hydroxycinnamaldehyde from Alpinia galanga extracts on human chondrocytes. Phytochemistry 2009; 70: 237-243
- 6 Chaiwongsa R, Ongchai S, Tangyuenyong S, Kongtawelert P, Panthong A, Reutrakul V. Chondroprotective potential of bioactive compounds of Zingiber cassumunar Roxb. against cytokine-induced cartilage degradation in explant culture. J Med Plant Res 2012; 6: 5204-5213
- 7 Altman RD, Marcussen KC. Effectiveness of a Zingiber officinale extract in the treatment of osteoarthritic pain. Focus Altern Complement Ther 2004; 9: 126-127
- 8 Langner E. Ginger: history and use. Adv Ther 1998; 15: 25-44
- 9 Shen CL, Hong KJ, Kim SW. Effects of ginger (Zingiber officinale Rosc.) on decreasing the production of inflammatory mediators in sow osteoarthrotic cartilage explants. J Med Food 2003; 6: 323-328
- 10 Suekawa M, Ishige A, Yuasa K, Sudo K, Aburada M, Hosoya E. Pharmacological studies on ginger. I. Pharmacological actions of pungent constituents, [6]-gingerol and [6]-shogaol. J Pharmacobiodyn 1984; 7: 836-848
- 11 Therkleson T. Ginger and Osteoarthritis. In: Chen Q. ed. Osteoarthritis-Diagnosis Treatment and Surgery. Rijeka, Croatia: InTech Open Science; 2012: 157-168
- 12 Kumar L, Chhibber S, Kumar R, Kumar M, Harjai K. Zingerone silences quorum sensing and attenuates virulence of Pseudomonas aeruginosa . Fitoterapia 2015; 102: 84-95
- 13 Young HY, Luo YL, Cheng HY, Hsieh WC, Liao JC, Peng WH. Analgesic and anti-inflammatory activities of [6]-gingerol. J Ethnopharmacol 2005; 96: 207-210
- 14 Bartley JP, Jacobs AL. Effects of drying on flavour compounds in Australian-grown ginger (Zingiber officinale). J Sci Food Agric 2000; 80: 209-215
- 15 Jolad SD, Lantz RC, Chen GJ, Bates RB, Timmermann BN. Commercially processed dry ginger (Zingiber officinale): composition and effects on LPS-stimulated PGE2 production. Phytochemistry 2005; 66: 1614-1635
- 16 Jolad SD, Lantz RC, Solyom AM, Chen GJ, Bates RB, Timmermann BN. Fresh organically grown ginger (Zingiber officinale): composition and effects on LPS-induced PGE2 production. Phytochemistry 2004; 65: 1937-1954
- 17 Peng F, Tao Q, Wu X, Dou H, Spencer S, Mang C, Xu L, Sun L, Zhao Y, Li H, Zeng S, Liu G, Hao X. Cytotoxic, cytoprotective and antioxidant effects of isolated phenolic compounds from fresh ginger. Fitoterapia 2012; 83: 568-585
- 18 Homandberg GA, Ummadi V, Kang H. High molecular weight hyaluronan promotes repair of IL-1β-damaged cartilage explants from both young and old bovines. Osteoarthritis Cartilage 2003; 1: 177-186
- 19 Haseeb A, Haqqi TM. Immunopathogenesis of osteoarthritis. Clin Immunol 2013; 146: 185-196
- 20 Cahue S, Sharma L, Dunlop D, Ionescu M, Song J, Lobanok T, King L, Poole AR. The ratio of type II collagen breakdown to synthesis and its relationship with the progression of knee osteoarthritis. Osteoarthritis Cartilage 2007; 15: 819-823
- 21 Chen WP, Wang YL, Tang JL, Hu PF, Bao JP, Wu LD. Morin inhibits interleukin-1 beta-induced nitric oxide and prostaglandin E-2 production in human chondrocytes. Int Immunopharmacol 2012; 12: 447-452
- 22 Furumatsu T, Ozaki T, Asahara H. Smad3 activates the Sox9-dependent transcription on chromatin. Int J Biochem Cell Biol 2009; 41: 1198-1204
- 23 Snelling S, Davidson R, Swingler T, Price A, Clark I. Dkk3 can prevent cartilage degradation and modulate TGFbeta and Wnt signalling. Osteoarthritis Cartilage 2012; 20: S10
- 24 Hong YH, Park CW, Kim HS, Won KC, Kim YW, Lee CK. Effects of hypoxia/ischemia on catabolic mediators of cartilage in a human chondrocyte, SW1353. Biochem Biophys Res Commun 2013; 431: 478-483
- 25 Henrotin YE, De Groote DD, Labasse AH, Gaspar SE, Zheng SX, Geenen VG, Reginster LJ. Effects of exogenous IL-1β, TNFα, IL-6, IL-8 and LIF on cytokine production by human articular chondrocytes. Osteoarthritis Cartilage 1996; 4: 163-173
- 26 Loo FA, Joosten LA, Van Lent PL, Arntz OJ, van den Berg WB. Role of interleukin-1, tumor necrosis factor α, and interleukin-6 in cartilage proteoglycan metabolism and destruction effect of in situ blocking in murine antigen- and zymosan-induced arthritis. Arthritis Rheum 1995; 38: 164-172
- 27 Kim MK, Chung SW, Kim DH, Kim JM, Lee EK, Kim JY, Ha YM, Kim YH, No JK, Chung HS, Park KY, Rhee SH, Choi JS, Yu BP, Yokozawa T, Kim YJ, Chung HY. Modulation of age-related NF-kappaB activation by dietary zingerone via MAPK pathway. Exp Gerontol 2010; 45: 419-426
- 28 Xie X, Sun S, Zhong W, Soromou LW, Zhou X, Wei M, Ren Y, Ding Y. Zingerone attenuates lipopolysaccharide-induced acute lung injury in mice. Int Immunopharmacol 2014; 19: 103-109
- 29 Tominaga M, Tominaga T. Structure and function of TRPV1. Pflugers Arch 2005; 451: 143-150
- 30 Sterner O, Szallasi A. Novel natural vanilloid receptor agonists: new therapeutic targets for drug development. Trends Pharmacol Sci 1999; 20: 459-465
- 31 OʼNeill LA. The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress. Immunol Rev 2008; 226: 10-18
- 32 Liacini A, Sylvester J, Li WQ, Huang W, Dehnade F, Ahmad M, Zafarullah M. Induction of matrix metalloproteinase-13 gene expression by TNF-α is mediated by MAP kinases, AP-1, and NF-κB transcription factors in articular chondrocytes. Exp Cell Res 2003; 288: 208-217
- 33 Morse D, Pischke SE, Zhou Z, Davis RJ, Flavell RA, Loop T, Otterbein SL, Otterbein LE, Choi AMK. Suppression of inflammatory cytokine production by carbon monoxide involves the JNK pathway and AP-1. J Biol Chem 2003; 278: 36993-36998
- 34 Roebuck KA. Oxidant stress regulation of IL-8 and ICAM-1 gene expression: differential activation and binding of the transcription factors AP-1 and NF-kappaB. Int J Mol Med 1999; 4: 223-230
- 35 Kapoor M, Martel PJ, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011; 7: 33-42
- 36 Mengshol JA, Vincenti MP, Brinckerhoff CE. IL-1 induces collagenase-3 (MMP-13) promoter activity in stably transfected chondrocytic cells: requirement for Runx-2 and activation by p38 MAPK and JNK pathways. Nucleic Acids Res 2001; 29: 4361-4372
- 37 Drozdov VN, Kim VA, Tkachenko EV, Varvanina GG. Influence of a specific ginger combination on gastropathy conditions in patients with osteoarthritis of the knee or hip. J Altern Complement Med 2012; 18: 583-588
- 38 Baskar V, Selvakumar K, Madhan R, Srinivasan G, Muralidharan M. Study on improving bioavailability ratio of anti-inflammatory compound from ginger through nano transdermal delivery. Asian J Pharm Clin Res 2012; 5: 241-246
- 39 Wann AKT, Mistry J, Blain EJ, Michael-Titus AT, Knight MM. Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation. Arthritis Res Ther 2010; 12: R207
- 40 Gebauer M, Saas J, Sohler F, Haag J, Söder S, Pieper M, Bartner E, Beninga J, Zimmer R, Aigner T. Comparison of the chondrosarcoma cell line SW1353 with primary human adult articular chondrocytes with regard to their gene expression profile and reactivity to IL-1β . Osteoarthritis Cartilage 2005; 13: 697-708
- 41 Rasmussen HN, Van HG, Rasmussen UF. Lactate dehydrogenase is not a mitochondrial enzyme in human and mouse vastus lateralis muscle. J Physiol 2002; 541: 575-580
- 42 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55-63
- 43 Farndale RW, Buttle DJ, Barrett AJ. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 1986; 883: 173-177
- 44 Phitak T, Pothacharoen P, Settakorn J, Poompimol W, Caterson B, Kongtawelert P. Chondroprotective and anti-inflammatory effects of sesamin. Phytochemistry 2012; 80: 77-88
- 45 Reddy GK, Enwemeka CS. A simplified method the analysis of hydroxyproline in biological tissues. Clin Biochem 1996; 29: 225-229
- 46 Király K, Lapveteläinen T, Arokoski J, Törrönen K, Módis L, Kiviranta I, Helminen HJ. Application of selected cationic dyes for the semiquantitative estimation of glycosaminoglycans in histological sections of articular cartilage by microspectrophotometry. Histochem J 1996; 28: 577-590