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Tehranolid and Artemisinin Effects on Ameliorating Experimental Autoimmune Encephalomyelitis by Modulating Inflammation and Remyelination

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Abstract

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. Artemisinin (ART) is a natural sesquiterpene lactone with an endoperoxide bond that is well-known for its anti-inflammatory effects in experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS. Tehranolide (TEH) is a novel compound with structural similarity to ART. In this study, we aimed to investigate the ameliorating effect of TEH on EAE development by targeting proteins and genes involved in this process and compare its effects with ART. Female C57BL/6 mice were immunized with MOG35–55. Twelve days post-immunization, mice were treated with 0.28 mg/kg/day TEH and 2.8 mg/kg/day ART for 18 consecutive days, and the clinical score was measured daily. The levels of pro-inflammatory and anti-inflammatory cytokines were assessed in mice serum and splenocytes by ELISA. We also evaluated the mRNA expression level of cytokines, as well as genes involved in T cell differentiation and myelination in the spinal cord tissue by qRT-PCR. Administration of TEH and ART significantly alleviated EAE signs. A significant reduction in IL-6 and IL-17 secretion and IL-17 and IL-1 gene expression in spinal cord were observed in the TEH-treated group. ART had similar or less significant effects. Moreover, TGF-β, IL-4, and IL-10 genes were stimulated by ART and TEH in the spinal cord, while the treatments did not affect IFN-γ expression. Both treatments dramatically increased the expression of FOXP3, GATA3, MBP, and AXL. Additionally, the T-bet gene was reduced after TEH administration. The compounds made no changes in RORγt, nestin, Gas6, Tyro3, and Mertk mRNA expression levels in the spinal cord. The study revealed that both TEH and ART can effectively modulate the genes responsible for inflammation and myelination that play a crucial role in EAE. Interestingly, TEH demonstrated a greater potency compared to ART and hence may have the potential to be evaluated in interventions for the management of MS.

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Data Availability

The data generated and analyzed during the current study are available from the corresponding author on a reasonable request.

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Acknowledgements

We would like to thank Dr. Farshid Noorbakhsh, Professor of immunology, Tehran University of Medical Sciences, for his helpful comments and suggestions. This study was financially supported by Shahid Beheshti University of Medical Sciences; grant number 43002915.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Niloufar Salehi & Shokoofe Noori

  2. Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran

    Mitra Nourbakhsh

  3. Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Mitra Nourbakhsh

  4. Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Hossein Rezaeizadeh

  5. School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Afshin Zarghi

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  1. Niloufar Salehi
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Contributions

N.S. performed the experimental work and wrote the manuscript; M.N. critically revised the manuscript; S.N. conceived the study, supervised the research, and analyzed the data. H.R contributed in the conduction of the research and data analysis. A.Z. supervised the manuscript for important intellectual content. All authors read and approved the final version of the manuscript.

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Correspondence to Shokoofe Noori.

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All animals were treated according to the guidelines for the Care and Use of Laboratory Animals and the experimental procedures were approved by the Animal Use Ethics Committee of Shahid Beheshti University of Medical Science.

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Salehi, N., Nourbakhsh, M., Noori, S. et al. Tehranolid and Artemisinin Effects on Ameliorating Experimental Autoimmune Encephalomyelitis by Modulating Inflammation and Remyelination. Mol Neurobiol 60, 5975–5986 (2023). https://doi.org/10.1007/s12035-023-03449-x

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