Polar extract of Curcuma longa protects cartilage homeostasis: possible mechanism of action

  • Chandrasekaran Chinampudur Velusami
  • Edwin Jothie Richard
  • Bharathi Bethapudi
Original Article

Abstract

Background

Curcuma longa has been well documented for managing joint inflammation and pain. The present study investigated the effect of polar extract of C. longa (NR-INF-02) on cartilage homeostasis in human articular chondrocytes knee (NHAC-kn) cells to understand its plausible mechanism of action.

Methods

Dysregulation of cartilage homeostasis was induced by IL-1β and H2O2. Modulating effects of NR-INF-02 on degradation markers viz., chondrocyte apoptosis, senescence, cytokine, eicosanoids, and cartilage synthesis markers viz., glycosaminoglycans and type II collagen degradation was evaluated in human articular chondrocytes knee (NHAC-kn) cells. Further, the effect of NR-INF-02 on lipopolysaccharide (LPS)-induced expression of NF-kB in RAW264.7 macrophages was investigated.

Results

NR-INF-02 significantly attenuated IL-1β-induced chondrocyte cytotoxicity, apoptosis and release of chondrocyte degradation markers such as IL-6, IL-8, COX-2, PGE2, TNF-α, ICAM-1 in NHAC-kn cells. Also, NR-INF-02 protected IL-1β-induced damage to synthesis markers such as glycosaminoglycans, type II collagen and further attenuated H2O2-induced chondrocyte senescence. In addition NR-INF-02 suppressed LPS-induced NF-kB expression in RAW264.7 cells.

Conclusions

NR-INF-02 protects cartilage homeostasis by maintaining the balance between synthesis and degradation of cartilage matrix.

Keywords

NR-INF-02 Curcuma longa Osteoarthritis Cartilage homeostasis Pain Senescence Turmacin 

Notes

Acknowledgements

The authors are thankful to Indo–Spanish Joint Programme, Department of Biotechnology (DBT) of India, Centre for the development of Industrial Technology (CDTI) of Spain for providing partial financial assistance to this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Anandakumar S, Joseph JA, Bethapudi B, Agarwal A, Jung E-B (2014) Anti-inflammatory effects of turmeric (Curcuma longa L.) extract on acute and chronic inflammation models. J Korean Soc Food Sci Nutr 43:612–617CrossRefGoogle Scholar
  2. Bauer DC, Hunter DJ, Abramson SB, Attur M, Corr M, Felson D et al (2006) Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthr Cartil 14:723–727.  https://doi.org/10.1016/j.joca.2006.04.001CrossRefPubMedGoogle Scholar
  3. Beg S, Swain S, Hasan H, Barkat M, Hussain MS (2011) Systematic review of herbals as potential anti-inflammatory agents: recent advances, current clinical status and future perspectives. Pharmacogn Rev 5:120–137.  https://doi.org/10.4103/0973-7847.91102CrossRefPubMedPubMedCentralGoogle Scholar
  4. Benito MJ, Veale DJ, FitzGerald O, van den Berg WB, Bresnihan B (2005) Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis 64:1263–1267.  https://doi.org/10.1136/ard.2004.025270CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bharathi B, Sasikumar M, Ramanaiah I, Deepak M, Chandrasekaran CV (2017) Bioactive Turmerosaccharides from Curcuma longa extracts (NR-INF-02): potential ameliorating effect on osteoarthritis pain. Pharmacogn Mag 13(Suppl S3):623–627.  https://doi.org/10.4103/pm.pm_465_16Google Scholar
  6. Carlo MD, Loeser RF (2003) Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheumatol 48:3419–3430.  https://doi.org/10.1002/art.11338CrossRefGoogle Scholar
  7. Chandrasekaran CV, Sundarajan K, Edwin JR, Gururaja GM, Mundkinajeddu D, Agarwal A (2013) Immune-stimulatory and anti-inflammatory activities of Curcuma longa extract and its polysaccharide fraction. Pharmacogn Res 5:71–79.  https://doi.org/10.4103/0974-8490.110527CrossRefGoogle Scholar
  8. Cheng W, Wu D, Zuo Q, Wang Z, Fan W (2013) Ginsenoside Rb1 prevents interleukin-1 beta induced inflammation and apoptosis in human articular chondrocytes. Int Orthop 37:2065–2070.  https://doi.org/10.1007/s00264-013-1990-6CrossRefPubMedPubMedCentralGoogle Scholar
  9. Choi CH, Kim TH, Sung YK, Choi CB, Na YI, Yoo H, Jun JB (2014) SKI306X inhibition of glycosaminoglycan degradation in human cartilage involves down-regulation of cytokine-induced catabolic genes. Korean J Intern Med 29:647–655.  https://doi.org/10.3904/kjim.2014.29.5.647CrossRefPubMedPubMedCentralGoogle Scholar
  10. Dai SM, Shan ZZ, Nakamura H, Masuko-Hongo K, Kato T, Nishioka K, Yudoh K (2006) Catabolic stress induces features of chondrocyte senescence through overexpression of caveolin 1: possible involvement of caveolin 1-induced down-regulation of articular chondrocytes in the pathogenesis of osteoarthritis. Arthritis Rheumatol 54:818–831.  https://doi.org/10.1002/art.21639CrossRefGoogle Scholar
  11. Gao Y, Liu S, Huang J, Guo W, Chen J, Zhang L et al (2014) The ECM-cell interaction of cartilage extracellular matrix on chondrocytes. Biomed Res Int 2014:648459.  https://doi.org/10.1155/2014/648459PubMedPubMedCentralGoogle Scholar
  12. Haseeb A, Chen D, Haqqi TM (2013) Delphinidin inhibits IL-1β-induced activation of NF-κB by modulating the phosphorylation of IRAK-1Ser376 in human articular chondrocytes. Rheumatology 52:998–1008.  https://doi.org/10.1093/rheumatology/kes363CrossRefPubMedPubMedCentralGoogle Scholar
  13. Henrotin Y, Priem F, Mobasheri A (2013) Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management. Springerplus 1:56.  https://doi.org/10.1186/2193-1801-2-56CrossRefGoogle Scholar
  14. Hwang HS, Kim HA (2015) Chondrocyte apoptosis in the pathogenesis of osteoarthritis. Int J Mol Sci 16:26035–26054.  https://doi.org/10.3390/ijms161125943CrossRefPubMedPubMedCentralGoogle Scholar
  15. Karatay S, Kiziltunc A, Yildirim K, Karanfil RC, Senel K (2004) Effects of different hyaluronic acid products on synovial fluid levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in knee osteoarthritis. Ann Clin Lab Sci 34:330–335PubMedGoogle Scholar
  16. Kienzle G, von Kempis J (1998) Vascular cell adhesion molecule 1 (CD106) on primary human articular chondrocytes: functional regulation of expression by cytokines and comparison with intercellular adhesion molecule 1 (CD54) and very late activation antigen 2. Arthritis Rheumatol 41:1296–1305.  https://doi.org/10.1002/1529-0131(199807)41:7CrossRefGoogle Scholar
  17. Lane NE, Brandt K, Hawker G, Peeva E, Schreyer E, Tsuji W, Hochberg MC (2011) OARSI-FDA initiative: defining the disease state of osteoarthritis. Osteoarthr Cartil 19:478–482.  https://doi.org/10.1016/j.joca.2010.09.013CrossRefPubMedGoogle Scholar
  18. Lee AS, Ellman MB, Yan D, Kroin JS, Cole BJ, van Wijnen AJ, Im HJ (2013) A current review of molecular mechanisms regarding osteoarthritis and pain. Gene 527:440–447.  https://doi.org/10.1016/j.gene.2013.05.069CrossRefPubMedPubMedCentralGoogle Scholar
  19. Liu Q, Lu Z, Wu H, Zheng L (2015) Chondroprotective effects of taurine in primary cultures of human articular chondrocytes. Tohoku J Exp Med 235:201–213.  https://doi.org/10.1620/tjem.235.201CrossRefPubMedGoogle Scholar
  20. López-Armada MJ, Caramés B, Lires-Deán M, Cillero-Pastor B, Ruiz-Romero C, Galdo F, Blanco FJ (2006) Cytokines, tumor necrosis factor-alpha and interleukin-1beta, differentially regulate apoptosis in osteoarthritis cultured human chondrocytes. Osteoarthr Cartil 14:660–669.  https://doi.org/10.1016/j.joca.2006.01.005CrossRefPubMedGoogle Scholar
  21. Madhu K, Chanda K, Saji MJ (2013) Safety and efficacy of Curcuma longa extract in the treatment of painful knee osteoarthritis: a randomized placebo controlled trial. Inflammopharmacology 21:129–136.  https://doi.org/10.1007/s10787-012-0163-3CrossRefPubMedGoogle Scholar
  22. Marcu KB, Otero M, Olivotto E, Borzi RM, Goldring MB (2010) NF-kappaB signaling: multiple angles to target OA. Curr Drug Targets 11:599–613CrossRefPubMedPubMedCentralGoogle Scholar
  23. Nakata K, Ono K, Miyazaki J, Olsen BR, Muragaki Y, Adachi E, Yamamura K et al (1993) Osteoarthritis associated with mild chondrodysplasia in transgenic mice expressing alpha 1 (IX) collagen chains with a central deletion. Proc Natl Acad Sci USA 90:2870–2874.  https://doi.org/10.1073/pnas.90.7.2870CrossRefPubMedPubMedCentralGoogle Scholar
  24. Pulai JI, Chen H, Im HJ, Kumar S, Hanning C, Hegde PS, Loeser RF (2005) NF-kappa B mediates the stimulation of cytokine and chemokine expression by human articular chondrocytes in response to fibronectin fragments. J Immunol 174:5781–5788CrossRefPubMedPubMedCentralGoogle Scholar
  25. Qin J, Liu Y, Liu J, Li J, Tan Y, Li X et al (2013) Effect of Angelica sinensis polysaccharides on osteoarthritis in vivo and in vitro: a possible mechanism to promote proteoglycans synthesis. Evid Based Complement Altern Med 2013:794761.  https://doi.org/10.1155/2013/794761Google Scholar
  26. Roman-Blas JA, Jimenez SA (2006) NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthr Cartil 14:839–948.  https://doi.org/10.1016/j.joca.2006.04.008CrossRefPubMedGoogle Scholar
  27. Saksena AK, Srivastava S, Khattri S, Kumar S (2016) Efficacy of Curcuma longa in osteoarthritis: association of IL-1β, IL-10 and MMP-9 with severity of disease. J Immunol 196:13Google Scholar
  28. Sandell L, Aigner T (2001) Articular cartilage and changes in arthritis: cell biology of osteoarthritis. Arthritis Res 3:107–113.  https://doi.org/10.1186/ar148CrossRefPubMedPubMedCentralGoogle Scholar
  29. Sokolove J, Lepus CM (2013) Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther Adv Musculoskelet Dis 5:77–94.  https://doi.org/10.1177/1759720X12467868CrossRefPubMedPubMedCentralGoogle Scholar
  30. Sophia Fox AJ, Bedi A, Rodeo SA (2009) The basic science of articular cartilage structure, composition, and function. Sports Health 1:461–468.  https://doi.org/10.1177/1941738109350438CrossRefPubMedPubMedCentralGoogle Scholar
  31. Srivastava S, Saksena AK, Khattri S, Kumar S, Dagur RS (2016) Curcuma longa extract reduces inflammatory and oxidative stress biomarkers in osteoarthritis of knee: a four-month, double-blind, randomized, placebo-controlled trial. Inflammopharmacology 24:377–388CrossRefPubMedGoogle Scholar
  32. Terry DE, Rees-Milton K, Pruss C, Hopwood J, Carran J, Anastassiades TP (2007) Modulation of articular chondrocyte proliferation and anionic glycoconjugate synthesis by glucosamine (GlcN), N-acetyl GlcN (GlcNAc) GlcN sulfate salt (GlcN.S) and covalent glucosamine sulfates (GlcN-SO4). Osteoarthr Cartil 15:946–956.  https://doi.org/10.1016/j.joca.2007.02.010CrossRefPubMedGoogle Scholar
  33. Wang P, Guan PP, Guo C, Zhu F, Konstantopoulos K, Wang ZY (2013) Fluid shear stress-induced osteoarthritis: roles of cyclooxygenase-2 and its metabolic products in inducing the expression of proinflammatory cytokines and matrix metalloproteinases. FASEB J 27:4664–4677.  https://doi.org/10.1096/fj.13-234542CrossRefPubMedPubMedCentralGoogle Scholar
  34. Wojdasiewicz P, Poniatowski ŁA, Szukiewicz D (2014) The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediat Inflamm 2014:561459.  https://doi.org/10.1155/2014/561459CrossRefGoogle Scholar
  35. Wu C, Zhao W, Zhang X, Chen X (2015) Neocryptotanshinone inhibits lipopolysaccharide-induced inflammation in RAW264.7 macrophages by suppression of NF-κB and iNOS signaling pathways. Acta Pharm Sin B 5:323–329.  https://doi.org/10.1016/j.apsb.2015.01.010CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Chandrasekaran Chinampudur Velusami
    • 1
  • Edwin Jothie Richard
    • 1
  • Bharathi Bethapudi
    • 1
  1. 1.Department of Biology, R&D CentreNatural Remedies Private LimitedBangaloreIndia

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