Efeito do Flavonoide crisina em modelos de doenças neurodegenerativas

Abstract

Neurodegenerative diseases are in particular pathologies with major social and economic impacts. Brain disorders are pathological conditions in which corrective surgery cannot be widely used, because of this, the treatments are based on medications that only relieve the symptoms. Several observational and epidemiological studies suggest that a diet rich in flavonoids improves cognitive function and prevents neurodegenerative disorders in humans. Chrysin is part of the flavone class of flavonoids and can be found naturally in honey, propolis and various plant species such as Passiflora coerulea. Chrysin generally exhibits various biological activities and pharmacological effects, including antioxidant, anti-inflammatory, anticancer, antiviral and neuroprotective activities.In this context, Parkinson's disease (PD) is a progressive neurodegenerative disorder commonly affecting elderly people worldwide. The PD is a neurodegenerative disorder characterized by progressive degeneration of the nigrostriatal dopaminergic pathway with substantial loss of substantia nigra pars compacta (SNpc) neurons and depletion of dopamine (DA). Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating neurodegenerative disease of the central nervous system (CNS). The MS is considered one of the most intriguing neurological diseases by virtue of its autoimmune, chronic character, frequency and tendency to approach young adults. In this study, the PD model used was the 6-Hydroxydopamine (6-OHDA), which has been used since the late 70s, hydroxylated DA analogue neurotoxin, when administered directly to the striatum of animals selectively destroys nigrostriatal dopaminergic neurons. We found a protective effect of chrysin at dose 10 mg/kg (intra gastric - i.g) on behavioral and cognitive alterations, increased enzymatic and non-enzymatic markers of oxidative stress and neuroinflammation. In addition, chrysin protected against changes in striatal dopamine (DA), 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. Experimentally the most commonly used animal model for the study of MS is the model denominated experimental autoimmune encephalomyelitis (EAE), an animal model of CNS disease, which is induced by immunization with myelin-derived antigens, used in the laboratory for the investigation of MS because it resembles this condition in several aspects. In this model chrysin at dose 20 mg/kg (i.g) reduced weight loss and attenuated clinical signs by model. Moreover, chrysin blunted the EAE-induced increase in histone deacetylase (HDCA) activity, glycogen synthase kinase-3β (GSK-3β) levels and proinflammatory cytokine levels as well as in the EAE-induced decrease in histone acetyltransferases 3 and 4 (HAT3, HAT4). The current work demonstrated the viii protective effect of chrysin against two models of neurodegenerative diseases, exposing chrysin as an important target for further studies. Expected that in the future the chrysin become a combat aid the MS and PD.