Ellagic acid ameliorates neuroinflammation and demyelination in experimental autoimmune encephalomyelitis: Involvement of NLRP3 and pyroptosis

Siamak Afshinmajd | Mehrdad Roghani | Tourandokht Baluchnejadmojarad | Ensie Azadi-Ahmadabadi | Elham Esmaeil-Jamaat | Javad Fahanik-Babaei | Marzieh Fakour | Farzane Fereidouni | Reihaneh Ghasemi-Tarie | Shahram Jalalzade-Ogvar | Vahid Khodashenas | Ashkan Sanaierad | Elham Zahedi | Zahra Kiasalari Reineh

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URL :   http://research.shahed.ac.ir/WSR/WebPages/Report/PaperView.aspx?PaperID=148059
Date :  2020/12/02
Publish in :    Journal of Chemical Neuroanatomy
DOI :  https://doi.org/doi.org/10.1016/j.jchemneu.2020.101891
Link :  http://dx.doi.org/doi.org/10.1016/j.jchemneu.2020.101891
Keywords :Multiple sclerosis Natural products Ellagic acid Experimental autoimmune encephalomyelitis Neuroinflammation

Abstract :

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Multiple sclerosis (MS) is presented as the most common autoimmune and demyelinating neurological disorder with incapacitating complications and with no definite therapy. Most treatments for MS mainly focus on attenuation of its severity and recurrence. To model MS reliably to study pathogenesis and efficacy of possible chemicals, experimental autoimmune encephalomyelitis (EAE) condition is induced in rodents. Ellagic acid is a neuroprotective polyphenol that can protect against demyelination. This study was planned and conducted to assess its possible beneficial effect in MOG-induced EAE model of MS with emphasis on uncovering its modes of action. Ellagic acid was given p.o. (at doses of 10 or 50 mg/kg/day) after development of clinical signs of MS to C57BL/6 mice immunized with MOG35−55. Results showed that ellagic acid can ameliorate severity of the disease and partially restore tissue level of TNFα, IL-6, IL-17A and IL-10. Besides, ellagic acid lowered tissue levels of NLRP3 and caspase 1 in addition to its mitigation of neuroinflammation, demyelination and axonal damage in spinal cord specimens of EAE group. As well, ellagic acid treatment prevented reduction of MBP and decreased GFAP and Iba1 immunoreactivity. Taken together, ellagic acid can decrease severity of EAE via amelioration of astrogliosis, astrocyte activation, demyelination, neuroinflammation and axonal damage that is partly related to its effects on NLRP3 inflammasome and pyroptotic pathway.