Avaliação dos efeitos da Licochalcona A e do trans-cariofileno sobre a encefalomielite autoimune experimental (EAE)

Abstract

The multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with features to be chronic, progressive, inflammatory and demyelinating. Due to the clinical and histopathological similarity with experimental autoimmune encephalomyelitis disease (EAE) this became a widely accepted study animal model of MS because both have pathophysiological processes involving Th1 cells and soluble pro-inflammatory cytokines such as Interferon-gamma (INF-γ), tumor necrosis factor alpha (TNF-α) and more recently Th17 cells, primarily producers of IL-17, oxygen free radicals as NO and H2O2 by phagocytic cells. Drugs currently used in fact act on these inflammatory markers but have many disadvantages such as high cost and/or pronounced adverse effects. Due to that, the search for new drugs to treat MS focuses on substances that are able to modulate the production of these inflammatory mediators with greater advantages to the pacient. In the present study EAE was induced in female mice C57BL6 lineage with the MOG35-55 and the animals were treated with Licochalcone A (isolated and purified from Glycyrhizza Inflata) in doses 15 and 30 mg/Kg/dia and with trans-caryophyllene (obtained commercially in doses of 25 and 50 mg/Kg/dia by gavage (oral administration) from day 10° until the peak of the clinical symptoms of the disease. To verify the effect of this treatment the following parameters were used: clinical evaluation, was made by a neurological score of symptoms and weighing; histopathological analysis, for hematoxylin and eosin staining of the brain and spinal cord tissue at the end of the experiment; production of NO, evaluated by Griess method; production of H2O2; by Pick Mizel, both in culture of peritoneal cells; quantification of IFN-γ, IL-17, TNF-α was made by ELISA on the surface of spleen cells culture. Both Licochalcone A, as mainly the trans-caryophyllene in higher doses caused significant reduction in neuroinflamação and demyelination in the CNS. The levels of NO, H2O2, IFN-γ, IL-17, TNF-α also showed sharp reduction being correlated with the improvement of clinical symptoms. The results suggest that the Licochalcone A and trans-caryophyllene can modulate the production of inflammatory mediators, interfering on the pathogenesis of EAE. Such substances may be important instruments for treatment of CNS demyelinating inflammatory diseases such as EAE, animal model more used for multiple sclerosis.