Title Investigation the Effects of Oleuropein on the Cytokines profile of Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis Patients

Authors

DOI:

https://doi.org/10.22100/jkh.v18i2.3109

Keywords:

Rheumatoid arthritis, TNF-α, Oleuropein, Il-4

Abstract

Introduction: Nowadays, synthetic drugs used to treat inflammatory diseases are of the slightest interest due to their potential side effects and serious adverse effects. Therefore, finding new treatment approaches, especially herbal medicines, could help manage inflammation disorders. Olive and its products (oleuropein), as both antioxidants and inflammatory inhibitors, can effectively reduce the inflammatory process. This study aimed to investigate the effects of oleuropein on the cytokines profile of peripheral blood mononuclear cells of rheumatoid arthritis patients.

Methods: A 5 ml blood sample was taken from 40 patients with RA. Peripheral blood mononuclear cells (PBMCs) were isolated from each sample using Ficoll. Then, it cultured in 24 well tissue culture plates with and without oleuropein and phytohemagglutinin (PHA). The concentration of TNF-α and IL-4 was evaluated in the supernatant of treated and non-treated cells using immunoassay after 72 hours. The results were analyzed using t-test and ANOVA.

Results: The results revealed a significant reduction of TNF-α in treated PBMCs with oleuropein compared to non-treated cells, especially in the 100 mg/ml of oleuropein (P<0.0001). In addition, a significant increase in IL-4 in a dose-dependent manner was indicated (P<0.0001).

Conclusion: Our findings demonstrated that oleuropein could effectively reduce the inflammation of inflammatory diseases, especially rheumatoid arthritis, by increasing the anti-inflammatory factor IL-4 production and decreasing the level of TNF.

References

Makuch S, Więcek K, Woźniak M. The immunomodulatory and anti-inflammatory effect of curcumin on immune cell populations, cytokines, and in vivo models of rheumatoid arthritis. Pharmaceuticals 2021;14:309. doi: 10.3390/ph14040309

Liang H-Y, Yin H-X, Li S-F, Chen Y, Zhao Y-J, Hu W, et al. Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities. Biomolecules 2022;12:1383. doi: 10.3390/biom12101383

Dupuis ML, Pagano MT, Pierdominici M, Ortona E. The role of vitamin D in autoimmune diseases: could sex make the difference? Biology of Sex Differences 2021;12:1-12. doi: 10.1186/s13293-021-00358-3

Lubberts E, van den Berg WB. Cytokines in the pathogenesis of rheumatoid arthritis and collagen-induced arthritis. Madame Curie Bioscience Database. 2013.

Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 2015;74:5-17. doi: 10.1016/j.cyto.2014.09.011

Morimoto C, Romain PL, Fox DA, Anderson P, Dimaggio M, Levine H, et al. Abnormalities in CD4+ T-lymphocyte subsets in inflammatory rheumatic diseases. The American Journal of Medicine 1988;84:817-25. doi: 10.1016/0002-9343(88)90058-7

Covas M, Esquerda A, García-Rico A, Mahy N. Peripheral blood T-lymphocyte subsets in autoimmune thyroid disease. Journal of Investigational Allergology & Clinical Immunology 1992;2:131-5.

Hsu AT, Lupancu TJ, Lee M-C, Fleetwood AJ, Cook AD, Hamilton JA, et al. Epigenetic and transcriptional regulation of IL4-induced CCL17 production in human monocytes and murine macrophages. Journal of Biological Chemistry 2018;293:11415-23. doi: 10.1074/jbc.RA118.002416

Cowan MM. Plant products as antimicrobial agents. Clinical Microbiology Reviews 1999;12:564-82. doi: 10.1128/CMR.12.4.564

Middleton E. Effect of plant flavonoids on immune and inflammatory cell function. Flavonoids in the Living System 1998:175-82. doi: 10.1007/978-1-4615-5335-9_13

Bianchi G, Pozzi N. 3, 4-Dihydroxyphenylglycol, a major C6-C2 phenolic in Olea europaea fruits. Phytochemistry 1994;35:1335-7. doi: 10.1016/S0031-9422(00)94849-0

Olmez E, Vural K, Gok S, Ozturk Z, Kayalar H, Ayhan S, et al. Olive leaf extract improves the atherogenic lipid profile in rats fed a high cholesterol diet. Phytotherapy Research 2015;29:1652-7. doi: 10.1002/ptr.5445

Iacono A, Gómez R, Sperry J, Conde J, Bianco G, Meli R, et al. Effect of oleocanthal and its derivatives on inflammatory response induced by lipopolysaccharide in a murine chondrocyte cell line. Arthritis & Rheumatism 2010;62:1675-82. doi: 10.1002/art.27437

Lucas L, Russell A, Keast R. Molecular mechanisms of inflammation. Anti-inflammatory benefits of virgin olive oil and the phenolic compound oleocanthal. Current Pharmaceutical Design 2011;17:754-68. doi: 10.2174/138161211795428911

Beauchamp GK, Keast RS, Morel D, Lin J, Pika J, Han Q, et al. Ibuprofen-like activity in extra-virgin olive oil. Nature 2005;437:45-6. doi: 10.1038/437045a

Haloui E, Marzouk B, Marzouk Z, Bouraoui A, Fenina N. Hydroxytyrosol and oleuropein from olive leaves: Potent anti-inflammatory and analgesic activities. Journal of Food, Agriculture & Environment 2011;9:128-33.

Fernandes J, Fialho M, Santos R, Peixoto-Placido C, Madeira T, Sousa-Santos N, et al. Is olive oil good for you? A systematic review and meta-analysis on anti-inflammatory benefits from regular dietary intake. Nutrition 2020;69:110559. doi: 10.1016/j.nut.2019.110559

Granato D, Blum S, Rössle C, Le Boucher J, Malnoë A, Dutot G. Effects of parenteral lipid emulsions with different fatty acid composition on immune cell functions in vitro. Journal of Parenteral and Enteral Nutrition 2000;24:113-8. doi: 10.1177/0148607100024002113

Rosignoli P, Fuccelli R, Fabiani R, Servili M, Morozzi G. Effect of olive oil phenols on the production of inflammatory mediators in freshly isolated human monocytes. The Journal of Nutritional Biochemistry 2013;24:1513-9. doi: 10.1016/j.jnutbio.2012.12.011

Zhang J-Y, Yang Z, Fang K, Shi Z-L, Ren D-H, Sun J. Oleuropein prevents the development of experimental autoimmune myocarditis in rats. International Immunopharmacology 2017;48:187-95. doi: 10.1016/j.intimp.2017.05.013

Giner E, Recio M-C, Rios J-L, Giner R-M. Oleuropein protects against dextran sodium sulfate-induced chronic colitis in mice. Journal of Natural Products 2013;76:1113-20. doi: 10.1021/np400175b

Tolosa L, Donato MT, Gómez-Lechón MJ. General cytotoxicity assessment by means of the MTT assay. Protocols in in vitro hepatocyte research: Springer; 2015. p. 333-48. doi: 10.1007/978-1-4939-2074-7_26

Wongwarawipat T, Papageorgiou N, Bertsias D, Siasos G, Tousoulis D. Olive oil-related anti-inflammatory effects on atherosclerosis: potential clinical implications. Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders) 2018;18:51-62. doi: 10.2174/1871530317666171116103618

Rosillo MÁ, Alarcón-de-la-Lastra C, Castejón ML, Montoya T, Cejudo-Guillén M, Sánchez-Hidalgo M. Polyphenolic extract from extra virgin olive oil inhibits the inflammatory response in IL-1β-activated synovial fibroblasts. British Journal of Nutrition 2019;121:55-62. doi: 10.1017/S0007114518002829

Rosillo MÁ, Alcaraz MJ, Sánchez-Hidalgo M, Fernández-Bolaños JG, Alarcón-de-la-Lastra C, Ferrándiz ML. Anti-inflammatory and joint protective effects of extra-virgin olive-oil polyphenol extract in experimental arthritis. The Journal of Nutritional Biochemistry 2014;25:1275-81. doi: 10.1016/j.jnutbio.2014.07.006

Scotece M, Gómez R, Conde J, Lopez V, Gómez-Reino JJ, Lago F, et al. Further evidence for the anti-inflammatory activity of oleocanthal: Inhibition of MIP-1α and IL-6 in J774 macrophages and in ATDC5 chondrocytes. Life Sciences 2012;91:1229-35. doi: 10.1016/j.lfs.2012.09.012

Cariello M, Contursi A, Gadaleta RM, Piccinin E, De Santis S, Piglionica M, et al. Extra-virgin olive oil from Apulian cultivars and intestinal inflammation. Nutrients 2020;12:1084. doi: 10.3390/nu12041084

Schuerwegh A, Dombrecht E, Stevens W, Van Offel J, Bridts C, De Clerck L. Influence of pro-inflammatory (IL-1α, IL-6, TNF-α, IFN-γ) and anti-inflammatory (IL-4) cytokines on chondrocyte function. Osteoarthritis and Cartilage 2003;11:681-7. doi: 10.1016/S1063-4584(03)00156-0

Ouyang W, Ranganath SH, Weindel K, Bhattacharya D, Murphy TL, William CS, et al. Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism. Immunity 1998;9:745-55. doi: 10.1016/S1074-7613(00)80671-8

Yamada P, Zarrouk M, Kawasaki K, Isoda H. Inhibitory effect of various Tunisian olive oils on chemical mediator release and cytokine production by basophilic cells. Journal of Ethnopharmacology 2008;116:279-87. doi: 10.1016/j.jep.2007.11.028

Puel C, Quintin A, Agalias A, Mathey J, Obled C, Mazur A, et al. Olive oil and its main phenolic micronutrient (oleuropein) prevent inflammation-induced bone loss in the ovariectomised rat. British Journal of Nutrition 2004;92:119-27. doi: 10.1079/BJN20041181

D'Oronzo S, Coleman R, Brown J, Silvestris F. Metastatic bone disease: Pathogenesis and therapeutic options: Up-date on bone metastasis management. Journal of Bone Oncology 2019;15:100205. doi: 10.1016/j.jbo.2018.10.004

Santangelo C, Vari R, Scazzocchio B, De Sanctis P, Giovannini C, D'Archivio M, et al. Anti-inflammatory activity of extra virgin olive oil polyphenols: which role in the prevention and treatment of immune-mediated inflammatory diseases? Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders) 2018;18:36-50. doi: 10.2174/1871530317666171114114321

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2023-11-26

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Title Investigation the Effects of Oleuropein on the Cytokines profile of Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis Patients. (2023). Knowledge and Health in Basic Medical Sciences, 18(2), Page:53-59. https://doi.org/10.22100/jkh.v18i2.3109

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