Document Type : Original Article
Authors
1 Department of Immunology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
2 Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran.
3 Traditional and Complementary Medicine Research Center (TCMRC), Arak University of Medical Sciences, Arak, Iran.
Abstract
Background: Experimental autoimmune encephalomyelitis (EAE), as an autoimmune disease in the central nervous system (CNS), is an animal model for multiple sclerosis (MS) mediated by T lymphocytes.
Objective: To investigate ginger extract’s effect on reducing inflammation and improving the symptoms in the EAE model.
Methods: The EAE was induced by injecting MOG35-55 and pertussis toxin into eight-week-old female C57BL6 mice. The mice were treated with an intraperitoneal injection of 300 mg/kg/day of hydroalcoholic extract of ginger for 21 days. The disease severity and weight changes were measured daily. Then, the mice spleens were removed; the gene expressions of interleukin (IL)-17, transforming growth factor beta (TGF-β), interferon-γ (IFN-γ), and tumor necrosis factor α (TNF-α) were analyzed by Real-time PCR and the percentage of regulatory T lymphocytes (Treg cells) was determined by flow cytometry. Serum nitric oxide and antioxidant capacity were measured, and brain tissue sections were prepared to investigate the leukocyte infiltration and plaque formation.
Results: The severity of symptoms in the intervention group was lower than in the control. The gene expression levels of inflammatory cytokines, including IL-17 (P=0.04) and IFN-γ (P=0.01), were reduced. The Treg cells increased significantly, and the serum nitric oxide level was lower in the ginger-treated group. There was no significant difference in lymphocyte infiltration in the brain between the two groups.
Conclusion: The present study indicated that ginger extract could effectively reduce inflammatory mediators and modulate immune responses in EAE.
Keywords
- Ömerhoca S, Akkaş SY, İçen NK. Multiple sclerosis: diagnosis and differential diagnosis. Archives of Neuropsychiatry. 2018;55:S1.
- Ortiz GG, Pacheco-Moisés FP, Macías-Islas MÁ, Flores-Alvarado LJ, Mireles-Ramírez MA, González-Renovato ED, et al. Role of the blood–brain barrier in multiple sclerosis. Arch Med Res. 2014;45:687-697.
- Dargahi N, Katsara M, Tselios T, Androutsou M-E, De Courten M, Matsoukas J, et al. Multiple sclerosis: immunopathology and treatment update. Brain Sci. 2017;7:78.
- Danikowski K, Jayaraman S, Prabhakar B. Regulatory T cells in multiple sclerosis and myasthenia gravis. J Neuroinflammation. 2017;14:1-16.
- Dungan LS, McGuinness NC, Boon L, Lynch MA, Mills KH. Innate IFN‐γ promotes development of experimental autoimmune encephalomyelitis: a role for NK cells and M1 macrophages. Eur J Immunol. 2014;44:2903-2917.
- Jadidi‐Niaragh F, Mirshafiey A. Th17 cell, the new player of neuroinflammatory process in multiple sclerosis. Scand J Immunol. 2011;74:1-13.
- Ebrahimimonfared M, Ganji A, Zahedi S, Nourbakhsh P, Ghasami K, Mosayebi G. Characterization of regulatory t-cells in multiple sclerosis patients treated with interferon beta-1a. CNS Neurol Disord Drug Targets. 2018;17:113-118.
- Bahrami M, Mosayebi G, Ghazavi A, Ganji A. Immunomodulation in Multiple Sclerosis by Phytotherapy. Curr Immunol Rev. 2020;16:28-36.
- Mirshafiey A, Aghily B, Namaki S, Razavi A, Ghazavi A, Ekhtiari P, et al. Therapeutic approach by Aloe vera in experimental model of multiple sclerosis. Immunopharmacol Immunotoxicol. 2010;32:410-415.
- Zhang F, Ma N, Gao YF, Sun LL, Zhang JG. Therapeutic effects of 6‐gingerol, 8‐gingerol, and 10‐gingerol on dextran sulfate sodium‐induced acute ulcerative colitis in rats. Phytother Res. 2017;31:1427-1432.
- Rahnama P, Montazeri A, Huseini HF, Kianbakht S, Naseri M. Effect of Zingiber officinale R. rhizomes (ginger) on pain relief in primary dysmenorrhea: a placebo randomized trial. BMC Complement Altern Med. 2012;12:1-7.
- Saeedifar AM, Mosayebi G, Ghazavi A, Ganji A. Synergistic Evaluation of Ginger and Licorice Extracts in a Mouse Model of Colorectal Cancer. Nutrition and Cancer. 2021 2021/07/03;73:1068-1078.
- Zhu J, Chen H, Song Z, Wang X, Sun Z. Effects of ginger (Zingiber officinale Roscoe) on type 2 diabetes mellitus and components of the metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med. 2018;2018.
- Kuo P-L, Hsu Y-L, Huang M-S, Tsai M-J, Ko Y-C. Ginger suppresses phthalate ester-induced airway remodeling. J Agric Food Chem. 2011;59:3429-3438.
- Jafarzadeh A, Nemati M. Therapeutic potentials of ginger for treatment of Multiple sclerosis: A review with emphasis on its immunomodulatory, anti-inflammatory and anti-oxidative properties. J Neuroimmunol. 2018;324:54-75.
- Saleem U, Amin S, Ahmad B, Azeem H, Anwar F, Mary S. Acute oral toxicity evaluation of aqueous ethanolic extract of Saccharum munja Roxb. roots in albino mice as per OECD 425 TG. Toxicol Rep. 2017;4:580-585.
- Mosayebi G, Soleyman MR. Changes in synaptic transmission and long-term potentiation induction as a possible mechanism for learning disability in an animal model of multiple sclerosis. Int Neurourol J. 2016;20:26.
- Ghazavi A, Mosayebi G, Salehi H, Abtahi H. Effect of ethanol extract of saffron (Crocus sativus L.) on the inhibition of experimental autoimmune encephalomyelitis in C57bl/6 mice. Pak J Biol Sci. 2009;12:690-695.
- Jafarzadeh A, Azizi S-V, Nemati M, Khoramdel-Azad H, Shamsizadeh A, Ayoobi F, et al. Ginger Extract Reduces the Expression of IL-17 and IL-23 in the Seraand Central Nervous System of EAEMice. Iran J Immunol. 2015;12:288-301.
- Ghazavi A, Mosayebi G. The mechanism of sesame oil in ameliorating experimental autoimmune encephalomyelitis in C57BL/6 mice. Phytother Res. 2012;26:34-38.
- Mosayebi G, Ghazavi A, Aghili B, Mirshafiei A. Immunomodulating activity of Aloe Vera in animal model of multiple sclerosis. Journal of Arak University of Medical Sciences. 2009;12:109-115.
- Yang J, Xu L. Elevated IL-23R Expression and Foxp3+ Rorγt+ Cells in Intestinal Mucosa During Acute and Chronic Colitis. Med Sci Monit. 2016;22:2785.
- Mosayebi G, Ghazavi A. Effect of vitamin E on the inhibition of experimental autoimmune encephalomyelitis in C57BL/6 mouse. Journal of Arak University of Medical Sciences. 2006;9:68-75.
- Palizvzn M, Khademi S, Ghazavi A, Mosayebi G. Correlation of two way active avoidance learning with Nitric Oxide and Ferric reduction/antioxidant power in rats. Journal of Arak University of Medical Sciences. 2006;9:1-8.
- Peiris M, Monteith GR, Roberts-Thomson SJ, Cabot PJ. A model of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice for the characterisation of intervention therapies. J Neurosci Methods. 2007;163:245-254.
- Ha SK, Moon E, Ju MS, Kim DH, Ryu JH, Oh MS, et al. 6-Shogaol, a ginger product, modulates neuroinflammation: a new approach to neuroprotection. Neuropharmacology. 2012;63:211-223.
- Al-Nahain A, Jahan R, Rahmatullah M. Zingiber officinale: A potential plant against rheumatoid arthritis. Arthritis. 2014;2014.
- Stoilova I, Krastanov A, Stoyanova A, Denev P, Gargova S. Antioxidant activity of a ginger extract (Zingiber officinale). Food Chem. 2007;102:764-770.
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