Alleviation of Experimental Allergic Encephalomyelitis in C57BL/6 Mice by Soy Daidzein


Experimental  allergic encephalomyelitis (EAE) is considered  as the murine model of multiple sclerosis. Daidzein a phytostrogenic compound of soy is known to impose immunomodulatory and antioxidative effects. We conducted this study to assess the potential protective and therapeutic effects of daidzein on allergic encephalomyelitis.
C57BL/6 mice  were induced  with  allergic encephalomyelitis  using  myelin oligodendrocyte glycoprotein (35-55) and received daidzein or dimethyl sulfoxide as the vehicle control. To assess the protective effect of daidzein, the mice were administered with 20 mg/kg of daidzein from 21 days prior to 21 days post EAE induction on a daily basis. To evaluate the therapeutic effect of daidzein, mice were fed with 300 mg/kg daidzein after the appearance of the first clinical signs for 10 days. One day after the last gavage, the mice were sacrificed. Spleen and brain were removed for further histological and immunological analysis.
Feeding mice with low dose of daidzein prior to disease induction did not affect disease severity.
However, treating with high dose of daidzein after the onset of the disease reduced interferon-γ and interleukin-12 secretion, enhanced interleukin-10 production, suppressed lymphocyte proliferation, and decreased cytotoxicity as judged by lactate dehydrogenase release.
In conclusion, daidzein reduced the extent of demyelination and disease severity. Chronic oral therapy with low dose of daidzein did not prevent experimental autoimmune encephalomyelitis. However, high doses of daidzein could prohibit disease exacerbation.

1. Togha M, Karvigh SA, Nabavi M, Moghadam NB, Harirchian MH, Sahraian MA, et al. Simvastatin treatment in patients with relapsing-remitting multiple sclerosis receiving interferon beta 1a: a double-blind randomized controlled trial. Mult Scler 2010; 16(7):848-54.

2. Cohen BA, Rieckmann P. Emerging oral therapies for multiple sclerosis. Int J Clin Pract 2007; 61(11):1922-30.

3. Tafreshi AP, Ahmadi A, Ghaffarpur M, Mostafavi H,Rezaeizadeh H, Minaie B, et al. An Iranian herbal-marine medicine, MS14, ameliorates experimental allergic encephalomyelitis. Phytother Res 2008; 22(8):1083-6.

4. Abdul-Majid KB, Wefer J, Stadelmann C, Stefferl A,Lassmann H, Olsson T, et al. Comparing the pathogenesis of experimental autoimmune encephalomyelitis in CD4-/- and CD8-/- DBA/1 mice defines qualitative roles of different T cell subsets. J Neuroimmunol 2003; 141(1-2):10-9.

5. Gold R, Linington C, Lassmann H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 2006;129(Pt 8):1953-71.

6. Polkowski K, Mazurek AP. Biological properties of genistein. A review of in vitro and in vivo data. Acta Pol Pharm 2000; 57(2):135-55.

7. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 1998; 139(10):4252-63.

8. Tyagi AM, Srivastava K, Sharan K, Yadav D, Maurya R, Singh D. Daidzein prevents the increase in CD4+CD28null T cells and B lymphopoesis in ovariectomized mice: a key mechanism for anti-osteoclastogenic effect. PLoS One 2011; 6(6):e21216.

9. Nakaya M, Yamasaki M, Miyazaki Y, Tachibana H, Yamada K. Estrogenic compounds suppressed interferon- gamma production in mouse splenocytes through direct cell-cell interaction. In Vitro Cell Dev Biol Anim 2003;39(8-9):383-7.

10. Mohammad-Shahi M, Haidari F, Rashidi B, Saei AA, Mahboob S, Rashidi M-R. Comparison of the effects of genistein and daidzein with dexamethasone and soy protein on rheumatoid arthritis in rats. BioImpacts 2011;1(3):161.

11. Mishra P, Kar A, Kale RK. Prevention of chemically induced mammary tumorigenesis by daidzein in pre- pubertal rats: the role of peroxidative damage and antioxidative enzymes. Mol Cell Biochem 2009; 325(1-2):149-57.

12. De Paula ML, Rodrigues DH, Teixeira HC, Barsante MM, Souza MA, Ferreira AP. Genistein down-modulates pro- inflammatory cytokines and reverses clinical signs of experimental autoimmune encephalomyelitis. Int Immunopharmacol 2008; 8(9):1291-7.

13. Castro SB, Junior CO, Alves CC, Dias AT, Alves LL,Mazzoccoli L, et al. Immunomodulatory effects and improved prognosis of experimental autoimmune encephalomyelitis after O-tetradecanoyl-genistein treatment. Int Immunopharmacol 2012; 12(2):465-70.

14. Yueh T, Chu H. The metabolic fate of daidzein. Scientia Sinica 1977; 20(4):513-21.

15. Zhang J, Snyder SH. Nitric oxide stimulates auto-ADP- ribosylation of glyceraldehyde-3-phosphate dehydrogenase. Proc Natl Acad Sci U S A 1992;89(20):9382-5.

16. Oyebamiji AI, Finlay TM, Hough RM, Hoghooghi V, Lim E-MF, Wong CH, et al. Characterization of migration parameters on peripheral and central nervous system T cells following treatment of experimental allergic encephalomyelitis with CRYAB. J Neuroimmunol 2013;259 (1-2): 66-74.

17. O'Connor RA, Taams LS, Anderton SM. Translational mini-review series on Th17 cells: CD4 T helper cells: functional plasticity and differential sensitivity to regulatory T cell-mediated regulation. Clin Exp Immunol 2010; 159(2):137-47.

18. Goverman J. Autoimmune T cell responses in the central nervous system. Nat Rev Immunol 2009; 9(6):393-407.

19. Ramagopalan SV, Dobson R, Meier UC, Giovannoni G.Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol 2010; 9(7):727-39.

20. Martinez Doncel A, Rubio A, Arroyo R, de las Heras V,Martin C, Fernandez-Arquero M, et al. Interleukin-10 polymorphisms in Spanish multiple sclerosis patients. J Neuroimmunol 2002; 131(1-2):168-72.

21. Lopez-Posadas R, Ballester I, Abadia-Molina AC, Suarez MD, Zarzuelo A, Martinez-Augustin O, et al. Effect of flavonoids on rat splenocytes, a structure-activity relationship study. Biochem Pharmacol 2008 15;76(4):495-506.

22. Haak S, Croxford AL, Kreymborg K, Heppner FL, Pouly S, Becher B, et al. IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice. J Clin Invest 2009; 119(1):61.

23. Chitnis T, Khoury SJ. Cytokine shifts and tolerance in experimental autoimmune encephalomyelitis. Immunol Res 2003; 28(3):223-39.

IssueVol 13, No 4 (2014) QRcode
Daidzein Experimental allergic encephalomyelitis (EAE) Immunomodulation Interferon-gamma Isoflavones Multiple sclerosis Soy

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How to Cite
Razeghi Jahromi S, Arrefhosseini SR, Ghaemi A, Alizadeh A, Moradi Tabriz H, Togha M. Alleviation of Experimental Allergic Encephalomyelitis in C57BL/6 Mice by Soy Daidzein. Iran J Allergy Asthma Immunol. 1;13(4):256-264.