Efeitos do β-cariofileno sobre a encefalomielite autoimune experimental (EAE): estudo imunoistoquímico em camundongos C57BL/6

Abstract

Introduction: Multiple sclerosis (MS) is the most prevalent inflammatory demyelinating disease of the central nervous system (CNS) in the world. Experimental autoimmune encephalomyelitis (EAE) is the established animal model for the study of pathogenesis and new therapies for MS. It has been shown that copaiba oil has anti-inflammatory and neuroprotective properties. β-caryophyllene (BCP), one of the most important sesquiterpenes of this oil, modulates expression of the transcription factor NF-κβ by stimulating the cannabinoid receptor 2 (CB2). Objective: The profiles of IL-17, T-bet and GATA-3 were avaliated in situ in CNS. In adition, the possible remyelination properties stimulated by BCP in C57BL/6 mice with EAE were investigated. Methods: EAE was induced in three groups of five female C57BL/6 mice, with administration of BCP in two groups (25 and 50 mg/kg/day) by gavage, after the tenth day of induction. At nine days of treatment the three groups were euthanized and the CNS was removed and preserved. In histological sections, the techniques of immunohistochemistry and staining by Weigert - Pal – Russel’s method for myelin were made. Results: For the BCP group (50 mg/kg/day) there was reduction of IL-17 in brain, cerebellum and medulla (p <0.05), decrease in T-bet (p <0.05) in medulla and cerebellum and increase of GATA-3 (p<0.05) in cerebellum. It was observed remyelination and better organization of myelin in both groups treated with BCP (p<0.001). For other results there was no statistical significance in comparison with EAE group (BCP 25mg/Kg/dia group). Conclusion: The present research allowed to verify the immunomodulatory effect of BCP on the inflammatory aspects of EAE in C57BL/6 mice in situ. Its clear effect on the decrease in IL-17 cytokine expression, the T-bet transcription factor, the strong remyelination presented, together with the increase in GATA-3 (cerebellum) demonstrated on tecidual level, confirms the therapeutic potential for the treatment of the inflammatory and demyelinating diseases, such as MS.