Downregulation of Matrix Metalloproteinase-13 by the Root Extract of Cyathula officinalis Kuan and its Constituents in IL-1β-treated Chondrocytes

Abstract

The roots of Cyathula officinalis Kuan are widely used in Chinese medicine for the treatment of inflammatory disorders. Here, the ability of C. officinalis Kuan to downregulate matrix metalloproteinase (MMP)-13 was examined since MMP-13 is an important enzyme for the degradation of the cartilage collagen matrix, especially under arthritic conditions. The ethanol extract of C. officinalis Kuan as well as the n-hexane and chloroform soluble fractions were found to potently inhibit MMP-13 induction in IL-1β-treated SW1353 cells, a human chondrosarcoma cell line, at 50–200 µg/mL. Activity-guided separation led to the isolation of six compounds, palmitic acid (1), β-sitosterol (2), α-spinasterol (3), atractylenolide I (4), 1,3-diacetoxy-tetradeca-6E,12E-dien-8,10-dyn (5), and N-trans-feruloyl-3-methyldopamine (6). Among these, 4 and 5 exhibited MMP-13 downregulating activity in IL-1β-treated SW1353 cells. And 4 also showed anti-oedematous activity against λ-carageenan-induced paw edema in mice at 20–200 mg/kg, p. o. The results of this study provide information that can help elucidate the action mechanism of C. officinalis Kuan. In addition, the results presented here suggest that C. officinalis Kuan and its constituents may have the potential for chondroprotection against cartilage degrading disorders.

Key words

matrix metalloproteinase (MMP)‐13 - Cyathula officinalis Kuan - Amaranthacea - cartilage degradation - atractylenolide I - 1,3‐diacetoxy‐tetradeca‐6E,12E‐dien‐8,10‐dyn

References

• 1 Martel-Pelletier T, Welsch D J, Pelletier J-P. Metalloproteinases and inhibitors in arthritic diseases.  Best Pract Res Clin Rheumatol. 2001;  15 805-829
• 2 Cawston T E, Wilson A J. Understanding the role of tissue degrading enzymes and their inhibitors in development and disease.  Best Pract Res Clin Rheumatol. 2006;  20 983-1002
• 3 The State Pharmacopoeia Commission of the People's Republic of China .Pharmacopoeia of the people's republic of China. Vol. 1 Beijing; Chemical Industry Press 2000: 28
• 4 Pouchert C J, Behenke J. The Aldrich Library of ¹³C- and ¹H-FT NMR spectra. Vol. 1 St. Louis; Aldrich Chemical Company, Inc. 1993
• 5 Kang S S, Sohn K H. The structure elucidation of natural compounds. Seoul; Seoul National University Press 2000
• 6 Endo K, Taguchi T, Taguchi H, Hikino H, Yamahara J, Fujimura H. Antiinflammatory principles of Atractylodes rhizomes.  Chem Pharm Bull. 1979;  27 2954-2958
• 7 Pachaly P, Lansing A, Sin K S. Constituents of Atractylis koreana.  Planta Med. 1989;  55 59-61
• 8 Bonlmann F, Ahmed M, Grenz M, King M R, Robinson H. Bisabolene derivatives and other constituents from Coreopsis species.  Phytochemistry. 1983;  22 2858-2859
• 9 Tanaka H, Nakamura T, Ichino K, Ito K. A phenolic amide from Actinodaphne longifolia.  Phytochemistry. 1989;  28 2516-2517
• 10 Li C Q, He L C, Dong H Y, Jin J Q. Screening for the anti-inflammatory activity of fractions and compounds from Atractylodes macrocephala Koidz.  J Ethnopharmacol. 2007;  114 212-217
• 11 Dong H, He L, Huang M, Dong Y. Anti-inflammatory components isolated from Atractylodes macrocephala Koidz.  Nat Prod Res. 2008;  22 1418-1427
• 12 El Mabrouck M, Sylvester J, Zafarullah M. Signaling pathways implicated in oncostatin M-induced aggrecanase-1 and matrix metalloproteinase-13 expression in human articular chondrocytes.  Biochim Biophys Acta. 2007;  1773 309-320
• 13 Mossman T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxic assays.  J Immunol Methods. 1983;  65 55-63
• 14 Winter C A, Risley E A, Nuss G W. Carrageenan-induced edema in the hindpaw of the rat as an assay for anti-inflammatory drugs.  Proc Soc Exp Biol Med. 1962;  111 544-547