Abstract
Osteoarthritis (OA) is a chronic degenerative joint disease with inflammatory component. It is associated with progressive histological alterations and disabling symptoms. Today, drugs such as glucocorticoids (GCs) and nonsteroidal anti-inflammatory drugs (NSIADs) are commonly employed for treatment of osteoarthritis, but have serious and life-threatening side effects. The aim of the current study is to evaluate the effects of escin on cyclooxygenase-2 (COX-2, isoform), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), interleukin-18 (IL-18), tumor necrosis factor-alpha (TNF-α), and nitric oxide (NO) (1), as well as prostaglandin E2 (PGE2) on inflammatory cells, similar osteoarthritis in synoviocytes, and monocytes/macrophages, and to compare it with dexamethasone (DEX) and ibuprofen (IBP). Synovial cells were isolated from synovial membrane of the radiocarpal joint cartilage of an 8-month-old Holstein cow. THP-1 cells were prepared from Pasteur Institute of Iran. Cells were cultivated and exposed to lipopolysaccharide (LPS) stimulation without, or in the presence of, DEX, IBP, or escin. The gene expressions of IL-1β, TNF-α, IL-18, COX-2, and iNOS were evaluated by real-time PCR. Concentrations of NO and PGE2 were measured by ELISA methods. Our cells secreted an increased amounts of IL-1β, TNF-α, IL-18, COX-2, iNOS, NO, and PGE2 in response to LPS stimulation in all conditions. Escin can quench the gene expression of COX-2, iNOS, IL-1β, IL-18, and TNF-α in synoviocyte cells and production of NO and PGE2 in monocyte/macrophage cells alike DEX and IBP. We can use from escin for the treatment of osteoarthritis as an anti-inflammatory agent in the latter but further studies to support the results from such a model are needed.
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References
Lane NE, Shidara K, Wise BL (2017) Osteoarthritis year in review 2016: clinical. Osteoarthr Cartil 25(2):209–215. https://doi.org/10.1016/j.joca.2016.09.025
Blaney Davidson EN, van Caam AP, van der Kraan PM (2017) Osteoarthritis year in review 2016: biology. Osteoarthr Cartil 25(2):175–180. https://doi.org/10.1016/j.joca.2016.09.024
Heidari B (2011) Knee osteoarthritis prevalence, risk factors, pathogenesis and features: part I. Caspian J Int Med 2(2):205–212
Felson DT, Zhang Y, Hannan MT, Naimark A, Weissman BN, Aliabadi P, Levy D (1995) The incidence and natural history of knee osteoarthritis in the elderly, the framingham osteoarthritis study. Arthritis Rheumatol 38(10):1500–1505
Srikanth VK, Fryer JL, Zhai G, Winzenberg TM, Hosmer D, Jones G (2005) A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis. Osteoarthr Cartil 13(9):769–781
Muraki S, Akune T, Oka H, Mabuchi A, En-Yo Y, Yoshida M, Saika A, Nakamura K, Kawaguchi H, Yoshimura N (2009) Association of occupational activity with radiographic knee osteoarthritis and lumbar spondylosis in elderly patients of population-based cohorts: a large-scale population-based study. Arthritis Rheum 61(6):779–786
Nelson AE, Braga L, Renner JB, Atashili J, Woodard J, Hochberg MC, Helmick CG, Jordan JM (2010) Characterization of individual radiographic features of hip osteoarthritis in African American and White women and men: the Johnston County Osteoarthritis Project. Arthritis Care Res 62(2):190–197
Fernandes JC, Martel-Pelletier J, Pelletier JP (2002) The role of cytokines in osteoarthritis pathophysiology. Biorheology 39(1–2):237–246
Okada Y, Nakanishi I, Kajikawa K (1981) Ultrastructure of the mouse synovial membrane. Development and organization of the extracellular matrix. Arthritis Rheum 24(6):835–843
Palmer RM, Hickery MS, Charles IG, Moncada S, Bayliss MT (1993) Induction of nitric oxide synthase in human chondrocytes. Biochem Biophys Res Commun 193(1):398–405
Geng Y, Blanco FJ, Cornelisson M, Lotz M (1995) Regulation of cyclooxygenase-2 expression in normal human articular chondrocytes. J Immunol 155(2):796–801
Day RO, Graham GG (2013) Non-steroidal anti-inflammatory drugs (NSAIDs). BMJ (Clin Res Ed) 346:f3195. https://doi.org/10.1136/bmj.f3195
Behrens F, Shepard N, Mitchell N (1975) Alterations of rabbit articular cartilage by intra-articular injections of glucocorticoids. J Bone Joint Surg Am 57(1):70–76
Nakamura M, Watanabe J, Ogawa R, Kanamura S (1997) Immunohistochemical localization of type II and type I collagens in articular cartilage of the femoral head of dexamethasone-treated rats. Histochem J 29(9):645–654
Singh H, Sidhu S, Chopra K, Khan MU (2017) The novel role of beta-aescin in attenuating CCl4-induced hepatotoxicity in rats. Pharm Biol 55(1):749–757. https://doi.org/10.1080/13880209.2016.1275023
Xiao GM, Wei J (2005) Effects of beta-Aescin on the expression of nuclear factor-kappaB and tumor necrosis factor-alpha after traumatic brain injury in rats. J Zhejiang Univ Sci B 6(1):28–32. https://doi.org/10.1631/jzus.2005.B0028
Wang H, Zhang L, Jiang N, Wang Z, Chong Y, Fu F (2013) Anti-inflammatory effects of escin are correlated with the glucocorticoid receptor/NF-kappaB signaling pathway, but not the COX/PGF2alpha signaling pathway. Exp Ther Med 6(2):419–422. https://doi.org/10.3892/etm.2013.1128
Xin W, Zhang L, Sun F, Jiang N, Fan H, Wang T, Li Z, He J, Fu F (2011) Escin exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vivo and in vitro. Phytomedicine 18(4):272–277. https://doi.org/10.1016/j.phymed.2010.08.013
Du Y, Song Y, Zhang L, Zhang M, Fu F (2016) Combined treatment with low dose prednisone and escin improves the anti-arthritic effect in experimental arthritis. Int Immunopharmacol 31:257–265. https://doi.org/10.1016/j.intimp.2016.01.006
Dijkstra G, Moshage H, van Dullemen HM, de Jager-Krikken A, Tiebosch AT, Kleibeuker JH, Jansen PL, van Goor H (1998) Expression of nitric oxide synthases and formation of nitrotyrosine and reactive oxygen species in inflammatory bowel disease. J Pathol 186(4):416–421. https://doi.org/10.1002/(sici)1096-9896(199812)186:4<416::aid-path201>3.0.co;2-u
Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE (1998) Cyclooxygenase in biology and disease. FASEB J 12(12):1063–1073
Luzzi R, Feragalli B, Belcaro G, Cesarone MR, Cornelli U, Dugall M, Hosoi M (2011) Aescin: microcirculatory activity. Effects of accessory components on clinical and microcirculatory efficacy. Panminerva Med 53(3 Suppl 1):51–55
Lanas A, Garcia-Tell G, Armada B, Oteo-Alvaro A (2011) Prescription patterns and appropriateness of NSAID therapy according to gastrointestinal risk and cardiovascular history in patients with diagnoses of osteoarthritis. BMC Med 9:38. https://doi.org/10.1186/1741-7015-9-38
Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352(11):1092–1102. https://doi.org/10.1056/NEJMoa050493
Raetz CR, Whitfield C (2002) Lipopolysaccharide endotoxins. Annu Rev Biochem 71:635–700. https://doi.org/10.1146/annurev.biochem.71.110601.135414
Kuo PC, Schroeder RA (1995) The emerging multifaceted roles of nitric oxide. Ann Surg 221(3):220–235
Kost SAH, Roner LA, Gray JG (1995) A cyclic adenosine 3,5-monophosphate signal is required for the induction of IL-1b by TNF-a in human monocytes. J Immunol 155:836–844
Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE (2007) Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation. Clin Exp Immunol 147(2):227–235. https://doi.org/10.1111/j.1365-2249.2006.03261.x
Wu MJ, Wang L, Ding HY, Weng CY, Yen JH (2004) Glossogyne tenuifolia acts to inhibit inflammatory mediator production in a macrophage cell line by downregulating LPS-induced NF-kappa B. J Biomed Sci 11(2):186–199. https://doi.org/10.1159/000076031
Olee T, Hashimoto S, Quach J, Lotz M (1999) IL-18 is produced by articular chondrocytes and induces proinflammatory and catabolic responses. J Immunol 162(2):1096–1100
Futani H, Okayama A, Matsui K, Kashiwamura S, Sasaki T, Hada T, Nakanishi K, Tateishi H, Maruo S, Okamura H (2002) Relation between interleukin-18 and PGE2 in synovial fluid of osteoarthritis: a potential therapeutic target of cartilage degradation. J Immunother 25(1):S61–S64
Li Y, Jiang JM, Yang DH, Wang FL, Mao ZX (2009) Determination of the concentrations of interleukin-18 and other cytokines in the synovial fluid in patients with osteoarthritis. Nan Fang Yi Ke Da Xue Xue Bao 29(4):729–731
Wang FL, Jiang JM, Wang F, Fu ZZ, Zhang ZF (2010) Expressions of interleukin 18 and prostaglandin E2 and their correlation in the synoviocytes of patients with osteoarthritis. Nan Fang Yi Ke Da Xue Xue Bao 30(4):731–733
Cho ML, Jung YO, Moon YM, Min SY, Yoon CH, Lee SH, Park SH, Cho CS, Jue DM, Kim HY (2006) Interleukin-18 induces the production of vascular endothelial growth factor (VEGF) in rheumatoid arthritis synovial fibroblasts via AP-1-dependent pathways. Immunol Lett 103(2):159–166
de Lange-Brokaar BJ, Ioan-Facsinay A, van Osch GJ, Zuurmond AM, Schoones J, Toes RE, Huizinga TW, Kloppenburg M (2012) Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthritis Cartilage/OARS, Osteoarthritis Res Soc 20(12):1484–1499
Farahat MN, Yanni G, Poston R, Panayi GS (1993) Cytokine expression in synovial membranes of patients with rheumatoid arthritis and osteoarthritis. Ann Rheum Dis 52(12):870–875
Massicotte F, Lajeunesse D, Benderdour M, Pelletier JP, Hilal G, Duval N, Martel-Pelletier J (2002) Can altered production of interleukin-1beta, interleukin-6, transforming growth factor-beta and prostaglandin E(2) by isolated human subchondral osteoblasts identify two subgroups of osteoarthritic patients. Osteoarthritis Cartilage/OARS, Osteoarthritis Res Soc 10(6):491–500
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Maghsoudi, H., Hallajzadeh, J. & Rezaeipour, M. Evaluation of the effect of polyphenol of escin compared with ibuprofen and dexamethasone in synoviocyte model for osteoarthritis: an in vitro study. Clin Rheumatol 37, 2471–2478 (2018). https://doi.org/10.1007/s10067-018-4097-z
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DOI: https://doi.org/10.1007/s10067-018-4097-z