The Effect of Aqueous Extract of Tarragon on Clinical Symptoms and T Cell Differentiation in Experimental Autoimmune Encephalomyelitis

  • Tayebeh Nowras Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
  • Mohammad Fereidouni Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
  • Hamidreza Safari Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
  • Mohsen Naseri Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
Keywords: Artemisia dracunculus, EAE, Tarragon, Th1 cells, Th17 cells, Treg cells

Abstract

Multiple sclerosis (MS) is one of the autoimmune diseases that affects the central nervous system (CNS) and causes myelin loss and axonal damage. Recent studies have shown the important role of autoreactive T cells in the pathogenesis of MS. One of the plants in the Astersa family, which has therapeutic benefits is Artemisia dracunculus L. or Tarragon. In this study, the role of aqueous extract of Tarragon in suppressing Th1 and Th17 cell differentiation and ameliorating experimental autoimmune encephalomyelitis (EAE) was investigated. EAE was induced in C57BL/6 female mice by Hook kit MOG35-55/CFA Emulsion PTX and one group was treated with Tarragon at a dose of 500 mg/kg. Mice were euthanized on day 33 post-immunization, spleens were removed for assessing Th1, Th17 and Treg cells by flow cytometry. We provided evidence that Tarragon (500 mg/kg) significantly ameliorated clinical scores of EAE. We did not observe significant alterations in T cell differentiation to Th1, Th17 or Treg in the spleen of mice during EAE. This is the first experimental evidence showing that administration of aqueous extract of Tarragon reduces the severity of EAE, but the protective effect of Tarragon is independent of alteration in T cells in the spleen. These results suggest other mechanisms for the effectiveness of this extract in improving the EAE process.

References

1. Frohman EM, Racke MK, Raine CS. Multiple sclerosis--the plaque and its pathogenesis. N Engl J Med 2006; 354(9):942-55.
2. Hemmer B, Kerschensteiner M, Korn T. Role of the innate and adaptive immune responses in the course of multiple sclerosis. Lancet Neurol 2015; 14(4):406-19.
3. Whitacre CC, Reingold SC, O'Looney PA. A gender gap in autoimmunity. Science 1999; 283(5406):1277-8.
4. Bjartmar C, Wujek J, Trapp B. Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J Neurol Sci 2003; 206(2):165-71.
5. McFarland HF, Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol 2007; 8(9):913.
6. Baker D, Amor S. Experimental autoimmune encephalomyelitis is a good model of multiple sclerosis if used wisely. Mult Scler Relat Disord 2014; 3(5):555-64.
7. Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol 2015; 15(9):545-58.
8. Brucklacher-Waldert V, Stuerner K, Kolster M, Wolthausen J, Tolosa E. Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis. Brain 2009; 132(Pt 12):3329-41.
9. Bettelli E, Sullivan B, Szabo SJ, Sobel RA, Glimcher LH, Kuchroo VK. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J Exp Med 2004; 200(1):79-87.
10. Robinson AP, Harp CT, et al. The experimental autoimmune encephalomyelitis (EAE) model of MS: utility for understanding disease pathophysiology and treatment. Handb Clin Neurol 2014; 122:178-89.
11. Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, Esiri MM, et al. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 2008; 172(1):146-55.
12. Jäger A, Dardalhon V, Sobel RA, Bettelli E, Kuchroo VK. Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol; 183(11):7169-77.
13. Komiyama Y, Nakae S, Matsuki T, Nambu A, Ishigame H, Kakuta S, et al. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol 2006; 177(1):566-73.
14. Kohm AP, Carpentier PA, Anger HA, Miller SD. Cutting edge: CD4+ CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J Immunol 2002; 169(9):4712-6.
15. Sakaguchi S, Wing K, Miyara M. Regulatory T cells–a brief history and perspective. Eur J Immunol 2007; 37(S1):S116-S23.
16. Wang J, Qi Y, Niu X, Tang H, Meydani SN, Wu D. Dietary naringenin supplementation attenuates experimental autoimmune encephalomyelitis by modulating autoimmune inflammatory responses in mice. J Nutr Biochem 2018; 54:130-9.
17. Ayoughi F, Marzegar M, Sahari MA, Naghdibadi H. Chemical Compositions of Essential Oils of Artemisia dracunculus L. and Endemic Matricaria chamomilla L.and an Evaluation of their Antioxidative Effects. Journal of Agricultural Science and Technology. 2011; 13(1):79-88.
18. Obolskiy D, Pischel I, Feistel B, Glotov N, Heinrich M. Artemisia dracunculus l.(Tarragon): A critical review of its traditional use, chemical composition, pharmacology, and safety. J Agric Food Chem 2011; 59(21):11367-84.
19. Saadali B, Boriky D, Blaghen M, Vanhaelen M, Talbi M. Alkamides from Artemisia dracunculus. Phytochemistry 2001; 58(7):1083-6.
20. Eisenman SW, Poulev A, Struwe L, Raskin I, Ribnicky DM. Qualitative variation of anti-diabetic compounds in different Tarragon (Artemisia dracunculus L.) cytotypes. Fitoterapia 2011; 82(7):1062-74.
21. Benli M, Kaya I, Yigit N. Screening antimicrobial activity of various extracts of Artemisia dracunculus L. Cell Biochem Funct 2007; 25(6):681-6.
22. Meepagala KM, Sturtz G, Wedge DE. Antifungal constituents of the essential oil fraction of Artemisia dracunculus L. Var. dracunculus. J Agric Food Chem 2002; 50(24):6989-92.
23. Zani F, Massimo G, Benvenuti S, Bianchi A, Albasini A, Melegari M, et al. Studies on the genotoxic properties of essential oils with Bacillus subtilis rec-assay and Salmonella/microsome reversion assay. Planta medica 1991; 57(3):237-41.
24. Wang ZQ, Ribnicky D, Zhang XH, Zuberi A, Raskin I, Yu Y, et al. An extract of Artemisia dracunculus L. enhances insulin receptor signaling and modulates gene expression in skeletal muscle in KK-A(y) mice. J Nutr Biochem 2011; 22(1):71-8.
25. Kordali S, Kotan R, Mavi A, Cakir A, Ala A, Yildirim A. Determination of the chemical composition and antioxidant activity of the essential oil of Artemisia dracunculus and of the antifungal and antibacterial activities of Turkish Artemisia absinthium, A. dracunculus, Artemisia santonicum, and Artemisia spicigera essential oils. J Agric Food Chem 2005; 53(24):9452-8.
26. Rezaei R, Hazrati Tappeh K, Seyyedi S, Mikaili P. The Anti-leishmanial Efficacy of Artemisia dracunculus Ethanolic Extract in Vitro and Its Effects on IFN-gamma and IL-4 Response. Iran J Parasitol 2017; 12(3):398-407.
27. Aggarwal S, Shailendra G, Ribnicky DM, Burk D, Karki N, Qingxia Wang MS. An extract of Artemisia dracunculus L. stimulates insulin secretion from beta cells, activates AMPK and suppresses inflammation. J Ethnopharmacol 2015; 170:98-105.
28. Pelisch N, Dan T, Ichimura A, Sekiguchi H, Vaughan DE, van Ypersele de Strihou C, et al. Plasminogen Activator Inhibitor-1 Antagonist TM5484 Attenuates Demyelination and Axonal Degeneration in a Mice Model of Multiple Sclerosis. PloS one 2015; 10(4):e0124510.
29. Ribnicky DM, Kuhn P, Poulev A, Logendra S, Zuberi A, Cefalu WT, et al. Improved absorption and bioactivity of active compounds from an anti-diabetic extract of Artemisia dracunculus L. Int J Pharm 2009; 370(1-2):87-92.
30. Hwang I, Ahn G, Park E, Ha D, Song JY, Jee Y. An acidic polysaccharide of Panax ginseng ameliorates experimental autoimmune encephalomyelitis and induces regulatory T cells. Immunol Lett 2011; 138(2):169-78.
31. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005; 201(2):233-40.
32. Zhang H, Podojil JR, Chang J, Luo X, Miller SD. TGF-β–Induced Myelin Peptide-Specific Regulatory T Cells Mediate Antigen-Specific Suppression of Induction of Experimental Autoimmune Encephalomyelitis. J Immunol 2010; 184(12):6629-36.
33. Zhu L, Chen H, Liu M, Yuan Y, Wang Z, Chen Y, et al. Treg/Th17 cell imbalance and IL-6 profile in patients with unexplained recurrent spontaneous abortion. Reprod Sci 2017; 24(6):882-90.
34. Lochner M, Wang Z, Sparwasser T. The Special Relationship in the Development and Function of T Helper 17 and Regulatory T Cells. Prog Mol Biol Transl Sci 2015; 136:99-129.
35. Li S, Vana A, Ribeiro R, Zhang Y. Distinct role of nitric oxide and peroxynitrite in mediating oligodendrocyte toxicity in culture and in experimental autoimmune encephalomyelitis. Neuroscience 2011; 184:107-19.
36. Lim S, Constantinescu C. Current and future disease‐modifying therapies in multiple sclerosis. Int J Clin Pract 2010; 64(5):637-50.
37. Haghmorad D, Mahmoudi MB, Salehipour Z, Jalayer Z, Momtazi Brojeni AA, Rastin M, et al. Hesperidin ameliorates immunological outcome and reduces neuroinflammation in the mouse model of multiple sclerosis. J Neuroimmunol 2017; 302:23-33.
38. Yang C, Lai W, Zhou J, Zheng X, Cai Y, Yang W, et al. Betaine Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Dendritic Cell–Derived IL-6 Production and Th17 Differentiation. J Immunol 2018; 200(4):1316-24.
39. Li W, Zhang Z, Zhang K, Xue Z, Li Y, Zhang Z, et al. Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-gamma/ROR-gammat Signaling. Mol Neurobiol 2016; 53(8):5356-66.
40. Shen R, Deng W, Li C, Zeng G. A natural flavonoid glucoside icariin inhibits Th1 and Th17 cell differentiation and ameliorates experimental autoimmune encephalomyelitis. Int Immunopharmacol 2015; 24(2):224-31.
41. Miyara M, Sakaguchi S. Natural regulatory T cells: mechanisms of suppression. Trends Mol Med 2007; 13(3):108-16.
42. Zheng Q, Yang T, Fang L, Liu L, Liu H, Zhao H, et al. Effects of Bu Shen Yi Sui Capsule on Th17/Treg cytokines in C57BL/6 mice with experimental autoimmune encephalomyelitis. BMC Complement Altern Med 2015; 15(1):60.
43. Zareie P, Connor B, La Flamme AC. Amelioration of experimental autoimmune encephalomyelitis by clozapine is not associated with defective CD4 T cell responses. J Neuroinflammation 2017; 14(1):68.
44. Ajami B, Bennett JL, Krieger C, McNagny KM, Rossi FM. Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat Neurosci 2011; 14(9):1142.
45. Brosnan C, Bornstein M, Bloom B. The effects of macrophage depletion on the clinical and pathologic expression of experimental allergic encephalomyelitis. J Immunol 1981; 126(2):614-20.
46. Tran EH, Hoekstra K, van Rooijen N, Dijkstra CD, Owens T. Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice. J Immunol 1998; 161(7):3767-75.
47. King IL, Dickendesher TL, Segal BM. Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease. Blood 2009; 113(14):3190-7.
48. Benveniste EN. Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J Mol Med (Berl) 1997; 75(3):165-73.
49. Froushani SM, Zarei L, Ghaleh HE, Motlagh BM. Estragole and methyl-eugenol-free extract of Artemisia dracunculus possesses immunomodulatory effects. Avicenna J Phytomed 2016; 6(5):526-34.
50. Mishra MK, Yong VW. Myeloid cells—targets of medication in multiple sclerosis. Nat Rev Neurol 2016; 12(9):539-51.
Published
2019-10-23
How to Cite
1.
Nowras T, Fereidouni M, Safari H, Naseri M. The Effect of Aqueous Extract of Tarragon on Clinical Symptoms and T Cell Differentiation in Experimental Autoimmune Encephalomyelitis. Iran J Allergy Asthma Immunol. 18(5):523-532.
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Original Article(s)