Immunomodulatory and Anti-Inflammatory Effects of Scrophularia megalantha Ethanol Extract on an Experimental Model of Multiple Sclerosis

Background and objectives: Scrophularia megalantha is a native Iranian plant. In folk remedies, the species of the genus are used to treat stomach ulcers, goiter, eczema, cancer, psoriasis, and gall; however, there is not much research about S. megalantha. The current study aimed at evaluating the therapeutic effect of Scrophularia megalantha, a medicinal plant of Iran, on myelin oligodendrocyte glycoprotein 35-55 (MOG)-induced experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis (MS). Methods: The ethanol 80% extract of S. megalantha aerial parts was prepared by maceration method. The extract (100 mg/kg/day) was administered to C57BL/6 mice immunized with MOG (35-55) for 7 days, 3 weeks after EAE induction. The mice brain was removed and Hematoxylin-Eosin (H&E) was used to stain the sections. Moreover, spleen mononuclear cells from extract-treated or non-treated of EAE model mice were stimulated with MOG peptide and then culture supernatants were evaluated for IFN-ɣ, IL-17 and IL-10 cytokines using Enzyme-Linked Immuno Sorbent Assay (ELISA) kits. Results: Based on the obtained results, treatment with Scrophularia megalantha areal part extract significantly reduced inflammatory cells infiltration in the central nervous system (CNS) and also the disease severity in the experimental model of MS. Also, findings of the current study indicated that treatment with this medicinal plant in EAE mice model significantly decreased inflammatory cytokines including IFN-ɣ and IL-17 and vice versa significantly increased IL-10 as anti-inflammatory cytokine compared with non-treated of EAE model mice group. Conclusion: Scrophularia megalantha attenuated EAE by suppressing IFN-ɣ and IL-17 production and also increasing IL-10 cytokine. These findings suggested that this medicinal plant has the anti-inflammatory and immunomodulatory effects.

[1]  A. Azadmehr,et al.  Analgesic Effect and Immunomodulation Response on Pro-Inflammatory Cytokines Production by Scrophularia megalantha Extract , 2014 .

[2]  A. Mirshafiey,et al.  Autoantigens and autoantibodies in multiple sclerosis. , 2013, Iranian journal of allergy, asthma, and immunology.

[3]  A. Afaghi,et al.  Inhibition of Pro-inflammatory Cytokines by Ethyl Acetate Extract of Scrophularia striata , 2013 .

[4]  M. Lopes,et al.  Intracellular signaling pathways modulated by phenolic compounds: application for new anti-inflammatory drugs discovery. , 2012, Current medicinal chemistry.

[5]  S. Sriram Role of glial cells in innate immunity and their role in CNS demyelination , 2011, Journal of Neuroimmunology.

[6]  F. Jadidi-Niaragh,et al.  Th17 Cell, the New Player of Neuroinflammatory Process in Multiple Sclerosis , 2011, Scandinavian journal of immunology.

[7]  D. Centonze,et al.  T Regulatory Cells Are Markers of Disease Activity in Multiple Sclerosis Patients , 2011, PloS one.

[8]  A. Afshari,et al.  Evaluation of in vivo immune response activity and in vitro anti-cancer effect by Scrophularia megalantha , 2011 .

[9]  M. Lynch,et al.  Infiltration of Th1 and Th17 cells and activation of microglia in the CNS during the course of experimental autoimmune encephalomyelitis , 2010, Brain, Behavior, and Immunity.

[10]  M. Khorramizadeh,et al.  Flavonoids, cinnamic acid and phenyl propanoid from aerial parts of Scrophularia striata , 2010, Pharmaceutical biology.

[11]  S. Park,et al.  Application of plant biotechnology in the medicinal plant, Rehmannia glutinosa Liboschitz , 2009 .

[12]  A. Afshari,et al.  Suppression of nitric oxide production in activated murine peritoneal macrophages in vitro and ex vivo by Scrophularia striata ethanolic extract. , 2009 .

[13]  J. Russo,et al.  Regulation of energy metabolism pathways by estrogens and estrogenic chemicals and potential implications in obesity associated with increased exposure to endocrine disruptors. , 2009, Biochimica et biophysica acta.

[14]  Fu-Tong Liu,et al.  Galectin-3 Deficiency Reduces the Severity of Experimental Autoimmune Encephalomyelitis1 , 2009, The Journal of Immunology.

[15]  Jianfei Yang,et al.  Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells , 2008, European journal of immunology.

[16]  H. Link,et al.  IL-12/IFN-gamma/NO axis plays critical role in development of Th1-mediated experimental autoimmune encephalomyelitis. , 2008, Molecular immunology.

[17]  P. Cabot,et al.  A model of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice for the characterisation of intervention therapies , 2007, Journal of Neuroscience Methods.

[18]  Yanghong Wu,et al.  Glia Maturation Factor Regulation of STAT Expression: A Novel Mechanism in Experimental Autoimmune Encephalomyelitis , 2007, Neurochemical Research.

[19]  G. Mosayebi,et al.  C57BL/6 The Effect of Vitamin D3 on the Inhibition of Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice , 2006 .

[20]  B. Becher,et al.  Antigen presentation in autoimmunity and CNS inflammation: how T lymphocytes recognize the brain , 2006, Journal of Molecular Medicine.

[21]  C. Teunissen,et al.  Macrophages and neurodegeneration , 2005, Brain Research Reviews.

[22]  E. Ongini,et al.  A nitric oxide releasing derivative of flurbiprofen inhibits experimental autoimmune encephalomyelitis , 2004, Journal of Neuroimmunology.

[23]  D. Naughton,et al.  Superoxide and hydrogen peroxide suppression by metal ions and their EDTA complexes. , 2004, Biochemical and biophysical research communications.

[24]  Alireza Minagar,et al.  Blood-brain barrier disruption in multiple sclerosis , 2003, Multiple sclerosis.

[25]  H. Przuntek,et al.  Induction of Apoptosis of CD4+ T Cells by Immunomodulatory Therapy of Multiple Sclerosis with Glatiramer Acetate , 2003, European Neurology.

[26]  R. Dai,et al.  Distinct immune regulation of the response to H-2b restricted epitope of MOG causes relapsing–remitting EAE in H-2b/s mice , 2003, Journal of Neuroimmunology.

[27]  Y. Saeki,et al.  IL-6 plays a crucial role in the induction phase of myelin oligodendrocyte glycoprotein 35–55 induced experimental autoimmune encephalomyelitis , 1999, Journal of Neuroimmunology.

[28]  O. Stuve,et al.  Interferon beta in the treatment of multiple sclerosis , 1998, Neurology.

[29]  Moses Rodriguez,et al.  Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor‐α in the central nervous system , 1997, European journal of immunology.

[30]  A. Fernández,et al.  Antiinflammatory effects of different extracts and harpagoside isolated from Scrophularia frutescens L. , 1996, Farmaco.

[31]  M. Recio,et al.  Structural Considerations on the Iridoids as Anti-Inflammatory Agents , 1994, Planta medica.

[32]  H. Weiner,et al.  Epitopes of myelin basic protein that trigger TGF-beta release after oral tolerization are distinct from encephalitogenic epitopes and mediate epitope-driven bystander suppression. , 1993, Journal of immunology.

[33]  G. Kreutzberg,et al.  Cytotoxicity of microglia , 1992, Journal of Neuroimmunology.

[34]  S. Miller,et al.  Induction of active and adoptive relapsing experimental autoimmune encephalomyelitis (EAE) using an encephalitogenic epitope of proteolipid protein , 1992, Journal of Neuroimmunology.

[35]  S. Waugh,et al.  Experimental autoimmune encephalomyelitis is exacerbated by IL-1 alpha and suppressed by soluble IL-1 receptor. , 1991, Journal of immunology.

[36]  E. Benveniste,et al.  Induction and regulation of interleukin-6 gene expression in rat astrocytes , 1990, Journal of Neuroimmunology.

[37]  H. Kirchner,et al.  Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: Do cytokines trigger off exacerbations? , 1988, Acta neurologica Scandinavica.

[38]  J. Antel,et al.  Pathogenesis of multiple sclerosis , 1977, European journal of clinical investigation.

[39]  Bruce D. Trapp,et al.  Axonal degeneration and progressive neurologic disability in multiple sclerosis , 2009, Neurotoxicity Research.

[40]  Walter G. Bradley,et al.  Neurology in Clinical Practice , 1997 .

[41]  T. Owens,et al.  IFN-gamma shapes immune invasion of the central nervous system via regulation of chemokines. , 2000, Journal of immunology.