Journal of Food and Nutrition Research
ISSN (Print): 2333-1119 ISSN (Online): 2333-1240 Website: https://www.sciepub.com/journal/jfnr Editor-in-chief: Prabhat Kumar Mandal
Open Access
Journal Browser
Go
Journal of Food and Nutrition Research. 2022, 10(4), 313-320
DOI: 10.12691/jfnr-10-4-8
Open AccessArticle

Eucommia ulmoides Prevents Articular Cartilage Destruction via FPR2-LXA4 in the Rat Monoiodoacetate Model of Osteoarthritis

Doo ri Park1, Chang hwan Yeo1, Jee Eun Yoon1, Wan-Jin Jeon1, Woo-Jae Choung1 and In-Hyuk Ha1,

1Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 06110, Seoul, South Korea

Pub. Date: April 26, 2022

Cite this paper:
Doo ri Park, Chang hwan Yeo, Jee Eun Yoon, Wan-Jin Jeon, Woo-Jae Choung and In-Hyuk Ha. Eucommia ulmoides Prevents Articular Cartilage Destruction via FPR2-LXA4 in the Rat Monoiodoacetate Model of Osteoarthritis. Journal of Food and Nutrition Research. 2022; 10(4):313-320. doi: 10.12691/jfnr-10-4-8

Abstract

Osteoarthritis (OA) is a debilitating joint disorder with high incidence. Therapies for OA are currently lacking due to limited understanding of its pathogenesis. Eucommia ulmoides (EU) is a traditional herbal medicine used to treat OA, but the mechanisms underlying its disease-controlling effects are poorly understood. This study reports the anti-OA effects of an EU extract as well as underlying mechanisms in a rat model of OA. In rats, EU diminished articular cartilage destruction. Furthermore, MMP3, MMP13, and FPR2 levels were decreased in the rat articular cartilage and primary chondrocytes treated with EU extract. Moreover, EU treatment regulated the levels of inflammatory cytokines, prostaglandin E2 (PGE2), and lipoxin A4 (LXA4) in intra-articular lavage fluid. These results demonstrate that EU inhibits the progression of OA by suppressing the FPR2-LXA4 pathway to reduce inflammatory cytokines levels and block cartilage degeneration. Therefore, EU is a potential therapeutic agent for OA.

Keywords:
Eucommia ulmoides cartilage chondrocytes inflammation osteoarthritis

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]  Hootman, J. M., Helmick, C. G., “Projections of US prevalence of arthritis and associated activity limitations,” Arthritis. Rheum., 54, 226-229, 2006.
 
[2]  Goldring, M. B., Goldring, S. R., “Osteoarthritis,” J. Cell. Physiol., 213, 626-634, 2007.
 
[3]  Loeser, R. F., “Molecular mechanisms of cartilage destruction: mechanics, inflammatory mediators and aging collide,” Arthritis. Rheum., 54, 1357-1360, 2006.
 
[4]  Suri, S., Walsh, D. A., “Osteochondral alterations in osteoarthritis,” Bone, 51, 204-211, 2012.
 
[5]  Zhang, X., Xu, X., Xu, T., Qin, S., “β-Ecdysterone suppresses interleukin-1β-induced apoptosis and inflammation in rat chondrocytes via inhibition of NF-κB signaling pathway,” Drug. Dev. Res., 75, 195-201, 2014.
 
[6]  Latourte, A., Cherifi, C., Maillet, J., Ea, H., Bouaziz, W., Funck-Brentano, T., Cohen-Solal, M., Hay, E., Richette, P., “Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis,” Ann. Rheum. Dis., 76, 748-755, 2017.
 
[7]  Loeser, R. F., Goldring, S. R., Scanzello, C. R., Goldring, M. B., “Osteoarthritis: a disease of the joint as an organ,” Arthritis. Rheum., 64, 1697-1707, 2012.
 
[8]  Mobasheri, A., Rayman, M. P., Gualillo, O., Sellam, J., van der Kraan, P., Fearon, U., “The role of metabolism in the pathogenesis of osteoarthritis,” Nat. Rev. Rheumatol., 13, 302-311, 2017.
 
[9]  Cicuttini, F. M., Wluka, A. E., “Not just loading and age: the dynamics of osteoarthritis, obesity and inflammation,” Med. J. Aust., 204, 47, 2016.
 
[10]  Malfait, A. M., “Osteoarthritis year in review 2015: biology,” Osteoarthritis Cartilage, 24, 21-26, 2016.
 
[11]  Liu-Bryan, R., “Inflammation and intracellular metabolism: new targets in OA,” Osteoarthritis Cartilage, 23, 1835-1842, 2015.
 
[12]  Berenbaum, F., van den Berg, W. B., “Inflammation in osteoarthritis: changing views,” Osteoarthritis Cartilage, 23, 182-1824, 2015.
 
[13]  Serhan, C. N., Chiang, N., “Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus,” Br. J. Pharmacol., 153, S200-S215, 2008.
 
[14]  McMahon, B., Mitchell, S., Brady, H. R., Godson, C., “Lipoxins: revelations on resolution,” Trends. Pharmacol. Sci., 22, 391-395, 2001.
 
[15]  Sodin-Semrl, S., Taddeo, B., Tseng, D., Varga, J., Fiore, S., “Lipoxin A4 inhibits IL-1β-induced IL-6, IL-8, and matrix metalloproteinase-3 production in human synovial fibroblasts and enhances synthesis of tissue inhibitors of metalloproteinases,” J. Immunol., 164, 2660-2666, 2000.
 
[16]  Chan, M. M., Moore, A. R., “Resolution of Inflammation in Murine Autoimmune Arthritis Is Disrupted by Cyclooxygenase-2 Inhibition and Restored by Prostaglandin E 2-Mediated Lipoxin A4 Production,” J. Immunol. 184, 6418-6426, 2010.
 
[17]  Conte, F. P., Menezes-de-Lima, O. Jr., Verri, WA. Jr., Cunha, F. Q., Penido, C., Henriques, M. G., “Lipoxin A4 attenuates zymosan-induced arthritis by modulating endothelin-1 and its effects,” Br. J. Pharmacol., 161, 911-924, 2010.
 
[18]  Gierman, L. M., Wopereis, S., van El, B., Verheij, E. R., Werff-van der Vat, B. J. C., Bastiaan-sen-Jenniskens, Y. M., van Osch, G. J. V. M., Kloppenburg, M., Stojanovic-Susulic, V., Huizinga, T. W. J., et al., “Metabolic Profiling Reveals Differences in Concentrations of Oxylipins and Fatty Acids Secreted by the Infrapatellar Fat Pad of Donors With End-Stage Osteoarthritis and Normal Donors,” Arthritis. Rheum., 65, 2606-2614, 2013.
 
[19]  Krishnamoorthy, S., Recchiuti, A., Chiang, N., Yacoubian, S., Lee, C. H., Yang, R., Petasis, N. A., Serhan, C. N., “Resolvin D1 binds human phagocytes with evidence for proresolbing receptors,” Proc. Natl. Acad. Sci. U. S. A., 107, 1660-1665, 2010.
 
[20]  Brink, C., Dahlén, S., Drazen, J., Evans, J. F., Hay, D. W. P., Nicosia, S., Serhan, C. N., Shimizu, T., Yokomizo, T., “International Union of Pharmacology XXXVII. Nomenclature for leukotriene and lipoxin receptors,” Pharmacol. Rev., 55, 195-227, 2003.
 
[21]  Holmertz, A. S., Jonsson, C. A., Mohaddes, M., Lundqvist, C., Forsman, H., Gjertsson, I., Önn-heim, K., “Data describing expression of formyl peptide receptor 2 in human articular chondrocytes,” Data. Brief., 31, 105866, 2020.
 
[22]  József, L., Zouki, C., Petasis, N. A., Serhan, C. N., Filep, J. G., “Lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 inhibit peroxynitrite formation, NF-κB and AP-1 activation, and IL-8 gene expression in human leukocytes,” Proc. Natl. Acad. Sci. U. S. A., 99, 13266-13271, 2002.
 
[23]  Marcu, K. B., Otero, M., Olivotto, E., Borzi, R. M., Goldring, M. B., “NF-κB signaling: multiple angles to target OA,” Curr. Drug. Targets., 11, 599-613, 2010.
 
[24]  He, X., Wang, J., Li, M., Hao, D., Yang, Y., Zhang, C., He, R., Tao, R., “Eucommia ulmoides Oliv.: ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine,” J. Ethnopharmacol., 151, 78-92, 2014.
 
[25]  Hsieh, C. L., Yen, G. C., “Antioxidant actions of du-zhong (Eucommia ulmoides Oliv.) toward oxidative damage in biomolecules,” Life. Sci., 66, 1387-1400, 2000.
 
[26]  Kwan, C. Y., Chen, C., Deyama, T., Nishibe, S., “Endothelium-dependent vasorelaxant effects of the aqueous extracts of the Eucommia ulmoides Oliv. Leaf and bark: Implications on their antihypertensive action,” Vasc. Pharmacol., 40, 229-235, 2003.
 
[27]  Zhao, Y., Li, Y., Wang, X., Sun, W., “The experimental study of Cortex Eucommiae on meridian tropsim: The distribution study of aucubin in rat tissues,” J. Pharm. Biomed. Anal., 46, 368-373, 2008.
 
[28]  Lu, H., Jiang, J., Xie, G., Liu, W., Yan, G., “Effects of an aqueous extract of Eucommiae on articular cartilage in a rat model of osteoarthritis of the knee,” Exp. Ther. Med., 684-688, 2013.
 
[29]  Lee, S., Kwon, H., Lee, S., “SHINBARO, a new herbal medicine with multifunctional mechanism for joint disease: First therapeutic application for the treatment of osteoarthriti,” Arch. Pharm. Res., 34, 73-1777, 2011.
 
[30]  Kim, W. K., Chung, H., Pyee, Y., Choi, T. J., Park, H. J., Hong, J., Shin, J., Lee, J. H., Ha, I., Lee, S. K., “Effects of intra-articular SHINBARO treatment on monosodium iodoacetate-induced osteoarthritis in rats,” Chin. Med., 11, 17, 2016.
 
[31]  Lee, S. W., Song, Y. S., Shin, S. H., Kim, K. T., Park, Y. C., Park, B. S., Yun, I., Kim, K., Lee, S. Y., Chung, W. T., et al., “Cilostazol protects rat chondrocytes against nitric oxide-induced apoptosis in vitro and prevents cartilage destruction in a rat model of osteoarthritis,” Arthritis. Rheum., 58, 790-800, 2008.
 
[32]  Glasson, S. S., Chambers, M. G., Van Den Berg, W. B., Little, C. B., “The OARSI histopathology initiative–recommendations for histological assessments of osteoarthritis in the mouse,” Osteoarthritis Cartilage, 18, S17-S23, 2010.
 
[33]  Gosset, M., Berenbaum, F., Thirion, S., Jacques, C., “Primary culture and phenotyping of murine chondrocytes,” Nat. Protoc., 3, 1253-1260, 2008.
 
[34]  Yang, Y., Wang, Y., Kong, Y., Zhan, X., Bai, L., “The effects of different frequency treadmill exercise on lipoxin A4 and articular cartilage degeneration in an experimental model of monosodium iodoacetate-induced osteoarthritis in rats. Plos One, 12, e0179162, 2017.
 
[35]  Felson, D. T., “Developments in the clinical understanding of osteoarthritis,” Arthitis. Res. Ther., 11, 203, 2009.
 
[36]  Rannou, F., Pelletier, J. P., Martel-Pelletier, J., “Efficacy and safety of topical NSAIDs in the management of osteoarthritis: evidence from real-life setting trials and surveys,” Semin. Atrhtitis. Rheum., 45, S18-21, 2016.
 
[37]  Brizuela, N. Y., Montrull, H. L., Demurtas, S. L., Meirovich, C. I., “Articular cartilage in osteoarthritic patients: effects of declofenac, celecoxib and glucosamine sulfate on inflammatory markers,” Rev. Fac. Cien. Med. Univ. Nac. Cordoba., 64, 9-15, 2007.
 
[38]  Da Costa, B. R., Reichenbach, S., Keller, N., Nartey, L., Wandel, S., Jüni, P., Trelle, S., “Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: A network meta-analysis,” Lancet, 390, e21-e33, 2017.
 
[39]  Izzo, A. A., Kim, S. H., Radhakrishnan, R., Williamson, E. M., “A critical approach to evaluating clinical efficacy, adverse events and drug interactions of herbal remedies,” Phytother. Res., 30, 691-700, 2016.
 
[40]  Pfander, D., Heinz, N., Rothe, P., Carl, H., Swoboda, B., “Tenascin and aggrecan expression by articular chondrocytes is influenced by interleukin 1β: A possible explanation for the changes in matrix synthesis during osteoarthritis,” Ann. Rheum. Dis., 63, 240-244, 2004.
 
[41]  Meulenbelt, I., Seymour, A. B., Nieuwland, M., Huizinga, T. W. J., van Duijin, C. M., Slagboom, P. E., “Association of the interleukin-1 gene cluster with radiographic signs of osteoarthritis of the hip,” Arthritis. Rheum., 50, 1179-1186, 2004.
 
[42]  Sakkas, L. I., Johanson, N. A., Scanzello, C. R., Platsoucas, C. D., “Interleukin-12 is expressed by infiltrating macrophages and synovial lining cells in rheumatoid arthritis and osteoarthritis,” Cell. Immunol., 188, 105-110, 1998.
 
[43]  Scanzello, C. R., Umoh, E., Pessler, F., Diaz-Torne, C., Dicarlo, E., Potter, H. G., Mandl, L., Marx, R., Rodeo, S., Goldring, S. R., et al., “Local cytokine profiles in knee osteoarthritis: Elevated synovial fluid interleukin-15 differentiates early from end-stage disease,” Osteoarthritis Cartilage, 17, 1040-1048, 2009.
 
[44]  Campo, G. M., Avenoso, A., D’Ascola, A., Scuruchi, M., Prestipino, V., Calatroni, A., Campo, S., “Hyaluronan in part mediates IL-1β-induced inflammation in mouse chondrocytes by up-regulating CD44 receptors,” Gene, 494, 24-35, 2012.
 
[45]  Prockop, D. J., Kivirikko, K. I., “Collagens: Molecular biology, diseases, and potentials for therapy,” Annu. Rev. Biochem., 64, 403-434, 1995.
 
[46]  Chu, X. Q., Wang, J. J., Dou, L. D., Zhao, G., “Cartilage oligomeric matrix protein and matrix metalloproteinase-3 expression in the serum and joint fluid of a reversible osteoarthritis rabbit model,” Genet. Mol. Res., 14, 14207-14215, 2015.
 
[47]  Jiao, Q., Wei, L., Chen, C., Li, P., Wang, X., Li, Y., Guo, L., Zhang, C., Wei, X., “Cartilage oligomeric matrix protein and hyaluronic acid are sensitive serum biomarkers for early cartilage lesions in the knee joint,” Biomarkers, 21, 146-151, 2016.