Efeitos das antocianinas em modelos experimentais da doença de Alzheimer: estudos in vitro e in vivo

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive and irreversible decline in various intellectual functions of the individual. The main neuropathological features include extracellular plaque deposition formed by the β-amyloid peptide (Aβ) and the intracellular accumulation of neurofibrillary tangles. Moreover other factors have also been associated with the pathogenesis of AD such as oxidative stress, neuroinflammation, cholinergic signaling deficits, Na+,K+-ATPase dysfunction, and central nervous system (CNS) insulin resistance. Considering that the available drugs can only alleviate the symptoms the search for new treatments that can prevent, delay or treat the disease are fundamental. Anthocyanins belong to the group of flavonoids and have been described that have important biological activities as antioxidant, anti-inflammatory and neuroprotective actions. Thus, the objective of this study was to investigate the effect of treatment with anthocyanin-rich extract in in vitro and in vivo experimental models of AD. In the in vitro model, cultures of cortical astrocytes from neonatal rats exposed to lipopolysaccharide (LPS) and treated with anthocyanin rich extract (10, 30, 50 and 100 μg/mL) in two types of protocols: one of prevention and the other of reversal. In these protocols, parameters of cell viability and oxidative stress, and the activity of the acetylcholinesterase (AChE) were evaluated. The extract prevented and reversed the changes promoted by LPS as increased levels of reactive oxygen species (ROS) and nitrite, increased AChE activity, decreased superoxide dismutase (SOD) activity, thiol content and cell viability. In the in vivo study, the model of sporadic dementia of the Alzheimer type was performed by intracerebroventricular injection (ICV) of streptozotocin (STZ) in Wistar rats. The animals received anthocyanin-rich extract (200 mg/kg, oral) for 25 days. Behavioral memory parameters were evaluated through the object recognition test and the Y-maze test. Cerebral cortex and hippocampus were used to evaluate oxidative stress parameters and AChE and Na + K + ATPase activities. Anthocyanin treatment was able to prevent memory deficits and increase AChE and Na + K + ATPase activity in cerebral cortex and hippocampus in the STZ-induced damage. For oxidative stress parameters, STZ induced an increase in lipid peroxidation and a decrease in activity of the enzymes SOD, catalase (CAT) and glutathione peroxidase (GPx) in cerebral cortex. In the hippocampus, STZ induced an increase in ROS, nitrite, lipid peroxidation, and SOD activity and a decrease in CAT and GPx activity. Treatment with anthocyanins was able to reverse the oxidative damage induced by STZ. These findings demonstrated that anthocyanins promoted a glioprotective effect, contributing to the maintenance of astrocyte homeostasis, probably due to its antioxidant effect and the modulation of AChE, which could have favored the protection observed regarding the decrease in the deficit of memory, reinforcing the promising therapeutic potential of anthocyanins