Osteoarthritis (OA) is a degenerative joint disease in which focal cartilage destruction is one of the primary features. The present study aims to evaluate the effect of a Centella asiatica fraction on in vitro and in vivo cartilage degradation. Bovine cartilage explants and bovine chondrocytes cultured in alginate were stimulated with IL-1β in the presence or absence of different concentrations (2, 5 and 10 μg/ml) of a standardized Centella asiatica triterpenes (CAT) fraction. The CAT fraction inhibited the IL-1β-induced proteoglycan (PG) release and nitric oxide (NO) production by cartilage explants in a dose-dependent manner. The IL-1β-induced reduction in PG synthesis and proliferation of chondrocytes cultured in alginate were counteracted by the CAT fraction at a concentration of 10 μg/ml. In a zymosan-induced acute arthritis model, the CAT fraction inhibited PG depletion without modulating joint swelling and inflammatory cell infiltration. In conclusion, the present study demonstrated for the first time that the tested Centella asiatica fraction was able to inhibit the zymosan-induced cartilage degradation in vivo without affecting the zymosan-induced inflammatory cell infiltration and joint swelling. The in vitro data indicate that the cartilage protective activity might at least partially be induced by the inhibition of NO production. The overall results indicate a possible disease modifying osteoarthritic activity of the Centella asiatica fraction.
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References
1.
Dieppe PA, Lohmander LS. Pathogenesis and management of pain in osteoarthritis. Lancet365:965–973, 2005.
2.
Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, Kington RS, Lane NE, Nevitt MC, Zhang Y, Sowers M, McAlindon T, Spector TD, Poole AR, Yanovski SZ, Ateshian G, Sharma L, Buckwalter JA, Brandt KD, Fries JF. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med133: 635–646, 2000.
3.
Martel-Pelletier J, Boileau C, Pelletier JP, Roughley PJ. Cartilage in normal and osteoarthritis conditions. Best Pract Res Clin Rheumatol22:351–384, 2008.
4.
Pelletier JP, DiBattista JA, Roughley P, McCollum R, Martel-Pelletier J. Cytokines and inflammation in cartilage degradation. Rheum Dis Clin North Am19:545–568, 1993.
5.
Shinmei M, Masuda K, Kikuchi T, Shimomura Y, Okada Y. Production of cytokines by chondrocytes and its role in proteoglycan degradation. J Rheumatol Suppl27:89–91, 1991.
6.
Stove J, Huch K, Gunther KP, Scharf HP. Interleukin-1beta induces different gene expression of stromelysin, aggrecan and tumor-necrosis-factor-stimulated gene 6 in human osteoarthritic chondrocytes in vitro. Pathobiology68:144–149, 2000.
7.
Mengshol JA, Vincenti MP, Coon CI, Barchowsky A, Brinckerhoff CE. Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor kappaB: differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum43:801–811, 2000.
8.
Attur MG, Patel IR, Patel RN, Abramson SB, Amin AR. Autocrine production of IL-1 beta by human osteoarthritis-affected cartilage and differential regulation of endogenous nitric oxide, IL-6, prostaglandin E2, and IL-8. Proc Assoc Am Physicians110:65–72, 1998.
9.
Pelletier JP, Jovanovic DV, Lascau-Coman V, Fernandes JC, Manning PT, Connor JR, Currie MG, Martel-Pelletier J. Selective inhibition of inducible nitric oxide synthase reduces progression of experimental osteoarthritis in vivo: possible link with the reduction in chondrocyte apoptosis and caspase 3 level. Arthritis Rheum43:1290–1299, 2000.
10.
Blom AB, van der Kraan PM, van den Berg WB. Cytokine targeting in osteoarthritis. Curr Drug Targets8:283–292, 2007.
11.
Hungin AP, Kean WF. Nonsteroidal anti-inflammatory drugs: overused or underused in osteoarthritis? Am J Med110:8S–11S, 2001.
12.
Ding C. Do NSAIDs affect the progression of osteoarthritis? Inflammation26:139–142, 2002.
13.
Pelletier JP, Martel-Pelletier J. DMOAD developments: present and future. Bull NYU Hosp Jt Dis65:242–248, 2007.
14.
Pei M, Yu C, Qu M. Expression of collagen type I, II and III in loose body of osteoarthritis. J Orthop Sci5:288–293, 2000.
15.
Nimni M, Deshmukh K. Differences in collagen metabolism between normal and osteoarthritic human articular cartilage. Science181:751–752, 1973.
16.
Schnabel M, Marlovits S, Eckhoff G, Fichtel I, Gotzen L, Vecsei V, Schlegel J. Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. Osteoarthritis Cartilage10:62–70, 2002.
17.
Brinkhaus B, Lindner M, Schuppan D, Hahn EG. Chemical, pharmacological and clinical profile of the East Asian medical plant Centella asiatica. Phytomedicine7:427–448, 2000.
18.
Lee J, Jung E, Kim Y, Park J, Hong S, Kim J, Hyun C, Kim YS, Park D. Asiaticoside induces human collagen I synthesis through TGFbeta receptor I kinase (TbetaRI kinase)-independent Smad signaling. Planta Med72:324–328, 2006.
19.
Shukla A, Rasik AM, Jain GK, Shankar R, Kulshrestha DK, Dhawan BN. In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica. J Ethnopharmacol65:1–11, 1999.
20.
Suguna L, Sivakumar P, Chandrakasan G. Effects of Centella asiatica extract on dermal wound healing in rats. Indian J Exp Biol34:1208–1211, 1996.
21.
Maquart FX, Chastang F, Simeon A, Birembaut P, Gillery P, Wegrowski Y. Triterpenes from Centella asiatica stimulate extracellular matrix accumulation in rat experimental wounds. Eur J Dermatol9: 289–296, 1999.
22.
Zheng CJ, Qin LP. Chemical components of Centella asiatica and their bioactivities. Zhong Xi Yi Jie He Xue Bao5:348–351, 2007.
23.
Farndale RW, Sayers CA, Barrett AJ. A direct spectrophotometric microassay for sulfated glycosaminoglycans in cartilage cultures. Connect Tissue Res9:247–248, 1982.
24.
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem126:131–138, 1982.
25.
Kruijsen MW, van den Berg WB, van de Putte LB, van den Broek WJ. Detection and quantification of experimental joint inflammation in mice by measurement of 99mTc-pertechnetate uptake. Agents Actions11: 640–642, 1981.
26.
Lens JW, van den Berg WB, van de Putte LB. Quantitation of arthritis by 99mTc-uptake measurements in the mouse knee-joint: correlation with histological joint inflammation scores. Agents Actions14:723–728, 1984.
27.
van den Berg WB, Kruijsen MW, van de Putte LB, van Beusekom HJ, van der Sluis-van der Pol M, Zwarts WA. Antigen-induced and zymosan-induced arthritis in mice: studies on in vivo cartilage proteoglycan synthesis and chondrocyte death. Br J Exp Pathol62: 308–316, 1981.
28.
van der Kraan PM, de Lange J, Vitters EL, van Beuningen HM, van Osch GJ, van Lent PL, van den Berg WB. Analysis of changes in proteoglycan content in murine articular cartilage using image analysis. Osteoarthritis Cartilage2:207–214, 1994.
29.
Farrell AJ, Blake DR, Palmer RM, Moncada S. Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann Rheum Dis51:1219–1222, 1992.
30.
Melchiorri C, Meliconi R, Frizziero L, Silvestri T, Pulsatelli L, Mazzetti I, Borzi RM, Uguccioni M, Facchini A. Enhanced and coordinated in vivo expression of inflammatory cytokines and nitric oxide synthase by chondrocytes from patients with osteoarthritis. Arthritis Rheum41:2165–2174, 1998.
31.
Vuolteenaho K, Moilanen T, Knowles RG, Moilanen E. The role of nitric oxide in osteoarthritis. Scand J Rheumatol36:247–258, 2007.
32.
van de Loo FA, Arntz OJ, van Enckevort FH, van Lent PL, van den Berg WB. Reduced cartilage proteoglycan loss during zymosan-induced gonarthritis in NOS2-deficient mice and in anti-interleukin-1-treated wild-type mice with unabated joint inflammation. Arthritis Rheum41:634–646, 1998.
33.
Guo JS, Cheng CL, Koo MW. Inhibitory effects of Centella asiatica water extract and asiaticoside on inducible nitric oxide synthase during gastric ulcer healing in rats. Planta Med70:1150–1154, 2004.
34.
Yun KJ, Kim JY, Kim JB, Lee KW, Jeong SY, Park HJ, Jung HJ, Cho YW, Yun K, Lee KT. Inhibition of LPS-induced NO and PGE(2) production by asiatic acid via NF-kappaB inactivation in RAW 264.7 macrophages: possible involvement of the IKK and MAPK pathways. Int Immunopharmacol8:431–441, 2008.
35.
Punturee K, Wild CP, Vinitketkumneun U. Thai medicinal plants modulate nitric oxide and tumor necrosis factor-alpha in J774.2 mouse macrophages. J Ethnopharmacol95:183–189, 2004.
36.
Aigner T, Rose J, Martin J, Buckwalter J. Aging theories of primary osteoarthritis: from epidemiology to molecular biology. Rejuvenation Res7:134–145, 2004.
37.
Aigner T, Hemmel M, Neureiter D, Gebhard PM, Zeiler G, Kirchner T, McKenna L. Apoptotic cell death is not a widespread phenomenon in normal aging and osteoarthritis human articular knee cartilage: a study of proliferation, programmed cell death (apoptosis), and viability of chondrocytes in normal and osteoarthritic human knee cartilage. Arthritis Rheum44:1304–1312, 2001.
