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Sinomenine Alleviates Murine Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis through Inhibiting NLRP3 Inflammasome

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Abstract

Multiple sclerosis (MS) is known as a chronic neuroinflammatory disorder typified by an immune-mediated demyelination process with ensuing axonal damage and loss. Sinomenine is a natural alkaloid with different therapeutic benefits, including anti-inflammatory and immunosuppressive activities. In this study, possible beneficial effects of sinomenine in an MOG-induced model of MS were determined. Sinomenine was given to MOG35–55-immunized C57BL/6 mice at doses of 25 or 100 mg/kg/day after onset of MS clinical signs till day 30 post-immunization. Analyzed data showed that sinomenine reduces severity of the clinical signs and to some extent decreases tissue level of pro-inflammatory cytokines IL-1β, IL-6, IL-18, TNFα, IL-17A, and increases level of anti-inflammatory IL-10. In addition, sinomenine successfully attenuated tissue levels of inflammasome NLRP3, ASC, and caspase 1 besides its reduction of intensity of neuroinflammation, demyelination, and axonal damage and loss in lumbar spinal cord specimens. Furthermore, immunoreactivity for MBP decreased and increased for GFAP and Iba1 after MOG-immunization, which was in part reversed upon sinomenine administration. Overall, sinomenine decreases EAE severity, which is attributed to its alleviation of microglial and astrocytic mobilization, demyelination, and axonal damage along with its suppression of neuroinflammation, and its beneficial effect is also associated with its inhibitory effects on inflammasome and pyroptotic pathways; this may be of potential benefit for the primary progressive phenotype of MS.

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Abbreviations

ASC:

apoptosis-associated speck-like protein containing a CARD

EAE:

experimental autoimmune encephalomyelitis

GFAP:

glial fibrillary acidic protein

Iba1:

ionized calcium binding adaptor molecule 1

IL-10:

interleukin 10

IL-17:

interleukin 17

IL-18:

interleukin 18

IL-6:

interleukin 6

MBP:

myelin basic protein

MOG35–55 :

myelin oligodendrocyte glycoprotein 35–55

MS:

multiple sclerosis

NLRP3:

NOD-, LRR-, and pyrin domain-containing 3

TNFα:

tumor necrosis factor α

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Funding

This research study was financially supported by a grant from the Deputy of Research and Technology of Ministry of Health and Medical Education (grant # 700-1850) in 2017.

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Authors and Affiliations

  1. Neurophysiology Research Center, Shahed University, Tehran, Iran

    Zahra Kiasalari, Siamak Afshin-Majd & Mehrdad Roghani

  2. Department of Physiology, School of Medicine, Iran University of Medical sciences, Tehran, Iran

    Tourandokht Baluchnejadmojarad & Mahsa Tashakori-Miyanroudi

  3. Department of Physiology, School of Medicine, Shahed University, Tehran, Iran

    Ensie Azadi-Ahmadabadi, Marzieh Fakour, Reihaneh Ghasemi-Tarie, Shahram Jalalzade-Ogvar, Vahid Khodashenas & Mehrdad Roghani

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  1. Zahra Kiasalari
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Correspondence to Mehrdad Roghani.

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Kiasalari, Z., Afshin-Majd, S., Baluchnejadmojarad, T. et al. Sinomenine Alleviates Murine Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis through Inhibiting NLRP3 Inflammasome. J Mol Neurosci 71, 215–224 (2021). https://doi.org/10.1007/s12031-020-01637-1

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