Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
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Anti-osteoarthritis Effects of the Combination of Boswellia serrata, Curcuma longa, and Terminalia chebula Extracts in Interleukin-1β-stimulated Human Articular Chondrocytes

  • Received : 2022.01.12
  • Accepted : 2022.03.28
  • Published : 2022.04.25
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Abstract

In this study, extracts of Boswellia serrata gum resin, Curcuma longa rhizome, and Terminalia chebula fruit were combined in different ratios, and their anti-osteoarthritis effects were compared to determine which combination had the best synergistic effect. B. serrata, C. longa, and T. chebula extracts in a 2:1:2 ratio exhibited higher antioxidative activity in scavenging DPPH radicals than did the individual extracts alone or the other extract combinations. Additionally, the 2:1:2 combination significantly improved the levels of enzymatic antioxidants and antioxidant-related proteins. Moreover, this same combination ratio decreased the protein levels of matrix metalloproteinase (MMP) 3 and MMP13 in interleukin-1β-stimulated human articular chondrocytes (HCHs) and increased those of aggrecan and collagen type II alpha 1 chain (COL2A1). Analysis of the underlying mechanisms revealed that the 2:1:2 combination significantly inhibited the phosphorylation of nuclear factor kappa B (NF-κB) p65, extracellular regulated protein kinase (ERK), and p38 mitogen-activated protein kinase (MAPK). Therefore, the 2:1:2 combination of these three plant extracts has the best potential for use as an effective dietary supplement for improving joint health compared with the individual extracts and their other combination ratios.

Keywords

Acknowledgement

The authors thank PLT Health Solutions (Morristown, NJ, USA) and Laila Nutraceuticals (Vijayawada, India) for providing samples, encouragement, and generous support.

References

  1. Lane NE, Shidara K, Wise BL. Osteoarthritis year in review 2016: Clinical Osteoarthr. Cartil 2017;25(2):209-15. https://doi.org/10.1016/j.joca.2016.09.025
  2. Haroyan A, Mukuchyan V, Mkrtchyan N, Minasyan N, Gasparyan S, Sargsyan A, et al. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med. 2018;18(1):1-16. https://doi.org/10.1186/s12906-017-2057-9
  3. Olivotto E, Otero M, Marcu KB. Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation. RMD Open. 2015;1(Suppl 1):e000061. https://doi.org/10.1136/rmdopen-2015-000061
  4. Van der Kraan PM, Van den Berg WB. Chondrocyte hypertrophy and osteoarthritis: Role in initiation and progression of cartilage degeneration? Osteoarthr Cartil. 2012;20(3):223-32. https://doi.org/10.1016/j.joca.2011.12.003
  5. Dreier R. Hypertrophic differentiation of chondrocytes in osteoarthritis: The developmental aspect of degenerative joint disorders. Arthritis Res Ther. 2010;12(5):216. https://doi.org/10.1186/ar3117
  6. Goldring SR, Goldring MB. The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res. 2004;427:s27-s36. https://doi.org/10.1097/01.blo.0000144854.66565.8f
  7. Kelwick R, Desanlis I, Wheeler GN, Edwards DR. The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family. Genome Biol. 2015;16(1):113. https://doi.org/10.1186/s13059-015-0676-3
  8. Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol. 2011;23(5):471. https://doi.org/10.1097/BOR.0b013e328349c2b1
  9. Santangelo K, Nuovo GJ, Bertone AL. In vivo reduction or blockade of interleukin-1β in primary osteoarthritis influences expression of mediators implicated in pathogenesis. Osteoarthr Cartil. 2012; 20(12):1610-8. https://doi.org/10.1016/j.joca.2012.08.011
  10. Kimmatkar N, Thawani V, Hingorani L, Khiyani R. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee-a randomized double-blind placebo-controlled trial. Phytomedicine. 2003;10(1):3-7. https://doi.org/10.1078/094471103321648593
  11. Daily JW, Yang M, Park S. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Med Food. 2016;19(8):717-29. https://doi.org/10.1089/jmf.2016.3705
  12. Seo JB, Jeong JY, Park JY, Jun EM, Lee SI, Choe SS, et al. Anti-Arthritic and Analgesic Effect of NDI10218, a Standardized Extract of Terminalia chebula, on Arthritis and Pain Model. Biomol Ther. 2012; 20(1):104-12. https://doi.org/10.4062/biomolther.2012.20.1.104
  13. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as ''Curecumin'': From kitchen to clinic. Biochem Pharmacol. 2008;75(4):787-809. https://doi.org/10.1016/j.bcp.2007.08.016
  14. Bag A, Bhattacharyya SK, Chattopadhyay RR. The development of Terminalia chebula Retz. (Combretaceae) in clinical research. Asian Pac J Trop Biomed. 2013;3(3):244-52. https://doi.org/10.1016/S2221-1691(13)60059-3
  15. Grover AK, Samson SE. Benefits of antioxidant supplements for knee osteoarthritis: Rationale and reality. Nutr J. 2016;15(1):1-13. https://doi.org/10.1186/s12937-015-0115-z
  16. Kim HL, Lee HJ, Lee DR, Choi BK, Yang SH. Anti-osteoarthritic Effects of an Herbal Composition LI73014F2 on Interleukin-1β-induced Primary Human Articular Chondrocytes. Molecules. 2020;25(9):2033. https://doi.org/10.3390/molecules25092033
  17. Kim HL, Lee HJ, Lee DR, Choi BK, Yang SH. Herbal Composition LI73014F2 Alleviates Articular Cartilage Damage and Inflammatory Response in Monosodium Iodoacetate-Induced Osteoarthritis in Rats. Molecules. 2020;25(22):5467. https://doi.org/10.3390/molecules25225467
  18. Lepetsos P, Papavassiliou AG. ROS/oxidative stress signaling in osteoarthritis. Biochim Biophys Acta 2016;1862(4):576-91. https://doi.org/10.1016/j.bbadis.2016.01.003
  19. Li D, Wang W, Xie G. Reactive oxygen species: the 2-edged sword of osteoarthritis. Am J Med Sci. 2012;344(6):486-90. https://doi.org/10.1097/MAJ.0b013e3182579dc6
  20. Henrotin Y, Kurz B, Aigner T. Oxygen and reactive oxygen species in cartilage degradation: friends or foes? Osteoarthr Cartil. 2005;13(8):643-54. https://doi.org/10.1016/j.joca.2005.04.002
  21. Regan EA, Bowler RP, Crapo JD. Joint fluid antioxidants are decreased in osteoarthritic joints compared to joints with macroscopically intact cartilage and subacute injury. Osteoarthr Cartil. 2008;16(4):515-21. https://doi.org/10.1016/j.joca.2007.09.001
  22. Sharma A, Upadhyay J, Jain A, Kharya MD, Namdeo A, Mahadik KR. Antioxidant activity of aqueous extract of Boswellia serrata. J Chem Biol Phys Sci. 2011;1:60-71.
  23. Tanvir EM, Hossen M, Hossain M, Afroz R, Gan SH, Khalil M, et al. Antioxidant properties of popular turmeric (Curcuma longa) varieties from Bangladesh. J Food Qual. 2017;2017:1-8.
  24. Hazra B, Sarkar R, Biswas S, Mandal N. Comparative study of the antioxidant and reactive oxygen species scavenging properties in the extracts of the fruits of Terminalia chebula, Terminalia belerica and Emblica officinalis. BMC Complement Altern Med. 2010;10(1):20. https://doi.org/10.1186/1472-6882-10-20
  25. Kulkarni RR, Patki PS, Jog VP, Gandage SG, Patwardhan B. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, crossover study. J Ethnopharmacol. 1991;33(1-2):91-5. https://doi.org/10.1016/0378-8741(91)90167-C
  26. Lekshmi PC, Arimboor R, Raghu KG, Menon AN. Turmerin, the antioxidant protein from turmeric (Curcuma longa) exhibits antihyperglycaemic effects. Nat Prod Res. 2012;26(17):1654-58. https://doi.org/10.1080/14786419.2011.589386
  27. Bag A, Kumar Bhattacharyya S, Kumar Pal N, Ranjan Chattopadhyay R. Anti-inflammatory, anti-lipid peroxidative, antioxidant and membrane stabilizing activities of hydroalcoholic extract of Terminalia chebula fruits. Pharm Biol. 2013;51(12):1515-20. https://doi.org/10.3109/13880209.2013.799709
  28. Li B, Jiang T, Liu H. Andrographolide protects chondrocytes from oxidative stress injury by activation of the Keap1-Nrf2-Are signaling pathway. J Cell Physiol. 2018;234(1):561-71. https://doi.org/10.1002/jcp.26769
  29. Chen JJ, Huang JF, Du WX, Tong PJ. Expression and significance of MMP3 in synovium of knee joint at different stage in osteoarthritis patients. Asian Pac J Trop Med. 2014;7(4):297-300. https://doi.org/10.1016/S1995-7645(14)60042-0
  30. Li NG, Shi ZH, Tang YP, Wang ZJ, Song SL, Qian LH, et al. New hope for the treatment of osteoarthritis through selective inhibition of MMP-13. Curr Med Chem. 2011;18(7):977-1001. https://doi.org/10.2174/092986711794940905
  31. Wu YS, Hu YY, Yang RF, Wang Z, Wei YY. The matrix metalloproteinases as pharmacological target in osteoarthritis: Statins may be of therapeutic benefit. Med Hypotheses. 2007;69(3):557-9. https://doi.org/10.1016/j.mehy.2007.01.042
  32. Mueller MB, Tuan RS. Anabolic/catabolic balance in pathogenesis of osteoarthritis: Identifying molecular targets. PM R. 2011;3(6):s3-s11. https://doi.org/10.1016/j.pmrj.2011.05.009
  33. Simkin PA. Rethinking the physiology of articular cartilage. Clin Rheumatol. 2009;15(5):260-3. https://doi.org/10.1097/RHU.0b013e3181b1d873
  34. Fan Z, Bau B, Yang H, Aigner T. IL-1 beta induction of IL-6 and LIF in normal articular human chondrocytes involves the ERK, p38 and NF kappa B signaling pathways. Cytokine 2004;28(1):17-24. https://doi.org/10.1016/j.cyto.2004.06.003
  35. Saklatvala J. Inflammatory signaling in cartilage: MAPK and NF-kappa B pathways in chondrocytes and the use of inhibitors for research into pathogenesis and therapy of osteoarthritis. Curr Drug Targets. 2008;8(2):305-13. https://doi.org/10.2174/138945007779940115
  36. Herrero-Beaumont G, Perez-Baos S, Sanchez-Pernaute O, Roman-Blas JA, Lamuedra A, Largo R. Targeting chronic innate inflammatory pathways, the main road to prevention of osteoarthritis progression. Biochem Pharmacol. 2019;165:24-32.
  37. Yang DW, Qian GB, Jiang MJ, Wang P, Wang KZ. Inhibition of microRNA-495 suppresses chondrocyte apoptosis through activation of the NF-kappaB signaling pathway by regulating CCL4 in osteoarthritis. Gene Ther. 2019;26(6):217-29. https://doi.org/10.1038/s41434-019-0068-5
  38. Abramson SB. Osteoarthritis and nitric oxide. Osteoarthr Cartil. 2008;16:s15-s20.2004;324(1):432-9. https://doi.org/10.1016/S1063-4584(08)60008-4