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

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.

• Authors: Zahra Kiasalari, Siamak Afshin-Majd, Tourandokht Baluchnejadmojarad, Ensie Azadi-Ahmadabadi, Marzieh Fakour, Reihaneh Ghasemi-Tarie, Shahram Jalalzade-Ogvar, Vahid Khodashenas, Mahsa Tashakori-Miyanroudi, Mehrdad Roghani
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 71 Issue 2 Pg. 215-224 (Feb 2021) ISSN: 1559-1166 [Electronic] United States
• PMID: 32812186 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Inflammasomes
• Morphinans
• Myelin-Oligodendrocyte Glycoprotein
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Peptide Fragments
• myelin oligodendrocyte glycoprotein (35-55)
• sinomenine

Topics

• Animals
• Astrocytes (drug effects)
• Body Weight
• Cytokines (analysis)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Encephalomyelitis, Autoimmune, Experimental (drug therapy, metabolism, pathology)
• Female
• Inflammasomes (antagonists & inhibitors)
• Mice
• Mice, Inbred C57BL
• Microglia (drug effects)
• Morphinans (administration & dosage, pharmacology, therapeutic use)
• Myelin-Oligodendrocyte Glycoprotein (immunology, toxicity)
• NLR Family, Pyrin Domain-Containing 3 Protein (antagonists & inhibitors)
• Peptide Fragments (immunology, toxicity)
• Pyroptosis (drug effects)
• Random Allocation
• Specific Pathogen-Free Organisms
• Spinal Cord (chemistry)