A Randomized, Triple-blind Placebo-controlled Trial to Determine the Effect of Saffron on the Serum Levels of MMP-9 and TIMP-1 in Patients with Multiple Sclerosis

  • Fatemeh Ghasemi Sakha Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
  • Amirreza Azimi Saeen Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  • Seyed Mohammad Moazzeni Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  • Farnaz Etesam Psychosomatic Medicine Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
  • Gholamhassan Vaezi Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
Keywords:
Matrix metalloproteinase 9, Multiple sclerosis, Saffron, Tissue inhibitor of metalloproteinases-1

Abstract

Matrix metalloproteinases (MMP)-9 facilitates the migration of T-cells to central nervous system (CNS), while tissue inhibitor of metalloproteinases-1(TIMP-1) inhibits the function of MMP-9. This study aimed to determine the appropriate treatment option for multiple sclerosis (MS).
Forty-three relapsing-remitting MS (RRMS) patients were randomly divided into two groups of 22 (group A, placebo) and 21 (group B, Saffron pill) individuals. Serum samples were collected from patients’ blood before using the Saffron pills/placebo pills and then after 12 months. The serum level of MMP-9 and its inhibitor, as well as TIMP-1, were measured by ELISA kits.
MMP-9 serum levels noticeably decreased in patients with MS following 12 months of treatment with Saffron pills (p=0.006) while the changes were not significant before and after 12 months of treatment with placebo pills. Although the levels of TIMP-1 increased significantly after one year treating with Saffron pills (p=0.0002), a considerable difference was not observed before and after taking the placebo pills.
The study finding revealed that 12-months treatment with Saffron could have a significant role in reducing the serum level of MMP-9 and increasing the serum level of TIMP-1 in RRMS patients. Therefore, modulating the serum levels of MMP-9 as an important regulator of T cell trafficking to the CNS might be a promising strategy in the treatment of MS patients.

Author Biography

Fatemeh Ghasemi Sakha, Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran

Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran

References

References

1. Pender, M.P. and J.M. Greer, Immunology of multiple sclerosis. Current allergy and asthma reports, 2007. 7(4): p. 285-292.

2. Kaye, E., Disorders primarily affecting white matter. Pediatric neurology principles and practice, 1999.

3. Compston, A. and A. Coles, Multiple sclerosis. The Lancet, 2008. 372(9648): p. 1502-1517.

4. Ebrahem, Q., et al., Increased neovascularization in mice lacking tissue inhibitor of metalloproteinases-3. Investigative ophthalmology & visual science, 2011. 52(9): p. 6117-6123.

5. Althoff, G.E., et al., Long-term expression of tissue-inhibitor of matrix metalloproteinase-1 in the murine central nervous system does not alter the morphological and behavioral phenotype but alleviates the course of experimental allergic encephalomyelitis. The American journal of pathology, 2010. 177(2): p. 840-853.

6. Prince, H.E., Biomarkers for diagnosing and monitoring autoimmune diseases. Biomarkers, 2005. 10(sup1): p. 44-49.

7. Christensen, O., J. Clausen, and T. Fog, Relationships between abnormal IgG index, oligoclonal bands, acute phase reactants and some clinical data in multiple sclerosis. Journal of neurology, 1978. 218(4): p. 237-244.

8. Glass-Marmor, L., et al., Immunomodulation by chronobiologically-based glucocorticoids treatment for multiple sclerosis relapses. Journal of neuroimmunology, 2009. 210(1): p. 124-127.

9. Lindberg, R.L., et al., The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis. Brain, 2001. 124(9): p. 1743-1753.

10. Waubant, E., et al., IFNβ lowers MMP-9/TIMP-1 ratio, which predicts new enhancing lesions in patients with SPMS. Neurology, 2003. 60(1): p. 52-57.

11. Waubant, E., et al., Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis. Neurology, 1999. 53(7): p. 1397-1397.

12. Trojano, M., et al., Changes of serum sICAM-1 and MMP-9 induced by rIFNβ-1b treatment in relapsing-remitting MS. Neurology, 1999. 53(7): p. 1402-1402.

13. Özenci, V., et al., Metalloproteinases and their tissue inhibitors in multiple sclerosis. Journal of autoimmunity, 1999. 12(4): p. 297-303.

14. Karabudak, R., et al., Effect of interferon β-1a on serum matrix metalloproteinase—9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in relapsing remitting multiple sclerosis patients. Journal of neurology, 2004. 251(3): p. 279-283.

15. YAZDANDOOST, H.S. and M. Taheri, Up regulation of MMP9 gene expression in female patients with multiple sclerosis. 2016.

16. Villoslada, P., Biomarkers for multiple sclerosis. Drug News Perspect, 2010. 23(9): p. 585-95.

17. Perry, V.H. and D. Anthony, Axon damage and repair in multiple sclerosis. Philosophical Transactions of the Royal Society of London B: Biological Sciences, 1999. 354(1390): p. 1641-1647.

18. Saman-Nezhad, B., et al., Epidemiological characteristics of patients with multiple sclerosis in Kermanshah, Iran in 2012. Journal of Mazandaran University of Medical Sciences, 2013. 23(104): p. 97-101.

19. Ramagopalan, S.V., et al., Multiple sclerosis: risk factors, prodromes, and potential causal pathways. The Lancet Neurology, 2010. 9(7): p. 727-739.

20. Javaid, M.A., et al., Matrix metalloproteinases and their pathological upregulation in multiple sclerosis: an overview. Acta Neurologica Belgica, 2013. 113(4): p. 381-390.

21. Alexander, J., et al., Alterations in serum MMP-8, MMP-9, IL-12p40 and IL-23 in multiple sclerosis patients treated with interferon-β1b. Multiple Sclerosis Journal, 2010. 16(7): p. 801-809.

22. Garcia‐Montojo, M., et al., Neutralizing antibodies, MxA expression and MMP‐9/TIMP‐1 ratio as markers of bioavailability of interferon‐beta treatment in multiple sclerosis patients: a two‐year follow‐up study. European journal of neurology, 2010. 17(3): p. 470-478.

23. Liuzzi, G., et al., Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple sclerosis: implication for pathogenesis. Multiple Sclerosis Journal, 2002. 8(3): p. 222-228.

24. Sastre-Garriga, J., et al., Decreased MMP-9 production in primary progressive multiple sclerosis patients. Multiple Sclerosis Journal, 2004. 10(4): p. 376-380.

25. Correale, J. and M.a.d.l.M.B. Molinas, Temporal variations of adhesion molecules and matrix metalloproteinases in the course of MS. Journal of neuroimmunology, 2003. 140(1): p. 198-209.

26. Fainardi, E., et al., Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis. Multiple Sclerosis Journal, 2006. 12(3): p. 294-301.

Published
2020-06-23
How to Cite
1.
Ghasemi Sakha F, Azimi Saeen A, Moazzeni SM, Etesam F, Vaezi G. A Randomized, Triple-blind Placebo-controlled Trial to Determine the Effect of Saffron on the Serum Levels of MMP-9 and TIMP-1 in Patients with Multiple Sclerosis. Iran J Allergy Asthma Immunol. 19(3):297-304.
Section
Original Article(s)