An investigation on the effects of Methanol extract of saffron on experimental autoimmune encephalomyelitis in C57BL/6 mice

Subject Areas : Developmental biology of plants and animals , development and differentiation in microorganisms

Shamila Eslambolchi ¹ (department of biology, Biology faculty, Islamic Azad University-North Tehran Branch, Tehran, I.R. Iran)
Mohammad-Hossein Sanati ² (Medical Genetic Laboratory, Medical Genetic Department, National Institute of Genetic Engineering and Biotechnology, Tehran, I.R. Iran)
Kamahldin Haghbin ³ (Biochemistry Laboratory, Plant bioproducts Department, National Institute of Genetic Engineering and Biotechnology, Tehran, I. R. Iran)

Received: 2022-12-25 Accepted : 2023-02-09 Published : 2024-08-24

Keywords: EAE, , MS, Saffron, MOG, C57BL/6 mice,

Abstract :

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of central nervous system and commonly used as an animal model for multiple sclerosis (MS). Multiple sclerosis is a disabling neurodegenerative disease in human being. Inflammation is a key event in both EAE and MS, which leads to demyelination and subsequent disability. It is shown that Crocus sativus L. stigma (saffron) extracts have anti-inflammatory activity in rats and mice. There are modern pharmacological evidences for anti-tumour, chemopreventive and genoprotective effects as well as radical scavenger properties of saffron extracts or its constituents. We observed that both therapeutic doses of dexamethasone and methanol extracts of saffron stigma at 100 mg/kg and more prevented EAE from progression significantly in pMOG-immunized female C57BL/6 mice. Aqueous maceration extract of Crocus sativus L. did not prevent EAE progression. These results suggest that saffron may attenuate symptoms of EAE by its anti-inflammatory activity. Experimental data analyzed by one-way ANOVA.

References:

1. 1. Soeda S., Ochiai T., Paopong L., Tanaka H., Shoyama Y., Shimeno H., Crocin suppresses tumour necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells. Life Sci. 2001 (69):2887-298
2. Deuvaux B., Enderlin F., Wallner B., Smilek DE., Induction of EAE with recombinent human MOG, and treatment of EAE with a MOG peptide. J Neuroimmunology 1997; (75):169-175
3. Ghazavi A., Mosayebi G., Salehi H., Abtahi H., Effects of ethanol extract of saffron (Crocus sativus L.) on inhibition of experimental autoimmune encephalomyelitis in C57Bl/6 mice. Pak J Biol. Sci. 2009 May; 12(9):690-695 doi:10.3023/pjbs.2009.690.695
4. Gommerman J.L., Giza K., Perper S., Sizing I., Ngam-ek A., Nickerson-Nutter C., Browning J.L., A role for surface lymphotoxin in experimental autoimmune encephalomyelitis independent of LIGHT. J clin Invest. 2003; (112):755-767
5. Probert L., Eugster H.P., Akassoglou K., Bauer J., Frei K., Lassmann H., Fontana A., TNFR1 signalling is critical for the development of demyelination and the limitation of T-cell responses during immune-mediated CNS disease. Brain 2000 (123):2005-2019
6. Linares D, Mana P, Goodyear M, Chow AM, Clavarino C, Huntington ND, Barnett L, Koentgen F., Tomioka R., Bernard C.C.A., Freier-Garabal M., Reid H.H., The magnitude and encephalitogenic potential of autoimmune response to MOG is enhanced in MOG deficient mice. J Outoimmun. 2003; (21):339-351
7. Voskuhl R.R., Mackenzie-Graham A., Chronic Experimental autoimmune encephalomyelitis is an excellent model to study neuroaxonal degeneration in multiple sclerosis. Frontiers in Molecular Neuroscience 2022 October; 01-12 doi; 103389/fnmol.2022.1024058
8. Faridi S., Delirezh N., Abtahi Froushani SM., beneficial effects of hydroalcoholic extract of saffron in alleviating experimental autoimmune diabetes in C57BL/6 mice. Iran J Allergy Asthma Immunol. 2019 February; 18(1):38-47
9. leadbetter E.A., Bourque C.R., Devaux B., Olson C.D., Sunshine G.H., Hirani S., Wallner B.P., Smilek D.E., Happ M.P., Experimental autoimmune encephalomyelitis induced with a combination of myelin oligodendrocyte glycoprotein is ameliorated by administration of a single myelin basic protein peptide. J immunol. 1998; (161):405-512
10. Part E., Martin R., The immunopathogenesis of multiple sclerosis. J Rehablit Res Devl 2002; (39):187-199
11. Paul C., Bolton C., Inhibition of blood brain barrier disruption in experimental allergic encephalomyelitis by short-term therapy with dexamethasone or cyclosporin A. Int J Immunopharmac 1995; (17):497-503
12. Gilgun-Sherki Y., Panet H., Holdengerber V., Mosberg-Galili R., Offen D., Axonal damage is reduced following glatiramer acetate treatment in C57/bl mice with chronic–induced experimental autoimmune encephalomyelitis. Neuroscience research 2003; (47) 201-207
13. Hosseinzadeh H., Younesi H.M., Antinociceptive and anti-inflammatory effects of crocus sativus L. Stigma and petal extracts in mice. BMC Pharmacol. 2002; (2):1-8
14. Poursamimi J., Shariati-Sarabi Z., Tavakkol-Afshari J., Mohajeri SA., Mohamadi M., Crocus sativus (saffron): An immunoregulatory factor in the autoimmune and non-autoimmune diseases. Iran J Allergy Asthma Immunol 2020 May; 19(supple-1):28-42
15. Rois J.L., Rico M.C., Ginger R.M., Manz S., An update review of saffron and its active constituents. Pytother Res. 1996 (10):189-193
16. Hosseinzadeh H., Khosravan V., Anticovulsant effects of aqueous and ethanolic extracts of Crocus sativus L. stigmas in mice. Arch Irn Med. 2002; (5):44-47
17. Hosseinzadeh H., Karimi G.H., Niapoor M., Antidepressant effects of crocus sativus stigma extracts and its constituents, crocin and safranal in mice. Acta Hort (ISHS) 2004; (650) 435-45
18. Abdullaev F.I., Cancer chemopreventive and tumoricidal properties of saffron (crocus sativus L.). Exptl Biol Med. 2002b; (227):20-25
19. Abe K, Sugiura M., Shoyama Y., Saito H., Crocin antagonizes ethanol inhibition of NMDA receptor-mediated responses in rat hippocampal neurons. Brain Research 1998; (787):132-138
20. Abe K, Sugiura M., Yamaguchi S., Shoyama Y., Saito H., Saffron extract prevents acetaldehyde-induced inhibition of long-term potentiation in rat dendate gyrus in vivo. Brain Research 1999; (581):287-289
21. Soeda S., Ochiai T., Paopong L., Tanaka H., Shoyama Y., Shimeno H., Crocin suppresses tumour necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells. Life Sci. 2001 (69):2887-298
22. Zhang Y.X., Sugiura M., Saito H., Shoyama, Y., Acute effects of Crocus Sativus L.on passive avoidance performance in mice. Biol Pharmachol Bull. 1994 (17):217-221
23. Soeda S., Ochiai T., Paopong L., Tanaka H., Shoyama Y., Shimeno H., Crocin suppresses tumour necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells. Life Sci. 2001 (69):2887-298
24. Nair S.C., Kurumboor S.K., Hasegawa J.H., Saffron chemopeventive in biology and medicine: a review. Cancer Biother. 1995; (10):257-264
25. Premkumar K., Abraham S.K., Santhiya S.T., Gopinath P.M., Ramesh A., Inhibition of genotixicity by saffron (Crocus sativus L.) in mice. Drug Chem Toxicol. 2001; (24):421-428
26. Premkumar K., Abraham S.K., Santhiya S.T., Ramesh A., protective effects of saffron (crocus sativus L.) on genotoxins-induced oxidative stress in swiss albino mice. Phytother Res. 2003; (17):614 –17
27. Hosseinzadeh H., Sadeghnia H.R., Safranal, a constituent of Crocus sativus (saffron) attenuated cerebral ischemia induced oxidative damege in rat hippocampus. J Pharm Pharmaceut Sci. 2005; (8):394-399
28. Gharagozloo M., Mace J.W., Calobresi P. A., Animal models to investigate the effects of inflammation on remyelination in multiple sclerosis. Frontiers in Molecular Neuroscience 2022 November; 01-10 doi:10.3389/fnmol.2022.995477
29. Ghazavi A., Mosayebi G., Salehi H., Abtahi H., Effects of ethanol extract of saffron (Crocus sativus L.) on inhibition of experimental autoimmune encephalomyelitis in C57Bl/6 mice. Pak J Biol. Sci. 2009 May; 12(9):690-695 doi:10.3023/pjbs.2009.690.695
30. Escribano J., Diaz-Guerra M.J.M., Reise H.H., Ontanon J., Garcia-Olmo D., Garcia-Olmo D.C., Robio A., Fernandez J.A., IN vitro activation of macrophages by a novel proteoglycan isolated from corms of crocus sativus L. Cancer Letters 1999; (144):107-114
31. Azari H., Ebrahimi S., Saeb s., Ghanbari A., et al., The effect of saffron aquatic extract and crocin on the differentiation of Neuralstem cells into oligodendrocyte precursor cells. Shiraz E-Medical Journal 2018 March;19(3): e60190
32. Moshiri M., Vahabzadeh M., Hosseinzadeh H., Clinical application of saffron (Crocus sativus) and its constituents: A Review. Drug Res. (stuttg) 2015 Jun; 65(6):287-295