Efeito neuroprotetor do extrato de amora preta (Rubus sp.) em mecanismos associados ao desenvolvimento e a progressão da Doença de Alzheimer: um estudo em modelos pré-clínicos

Abstract

Alzheimer's disease (AD) is a neurodegenerative, progressive and irreversible disease that leads to memory loss and cognitive decline. Among the pathophysiological mechanisms involved in AD, we can mention cholinergic deficit, neuroinflammation, oxidative stress, hyperphosphorylation of the Tau protein (p-Tau) and alterations in cerebral glucose metabolism. Considering that the drugs available for the treatment of AD only alleviate the symptoms, it is necessary to search for new pharmacological alternatives that can help in the prevention and progression of this disease. Blackberry (Rubus sp.) is a fruit rich in bioactive compounds, such as anthocyanins. Data from the literature have shown that the extract of this fruit has neuroprotective activity in different experimental models. Thus, the aim of this study was to evaluate the therapeutic potential of Rubus sp. in preclinical models of AD. Adult male Wistar rats were submitted to an experimental model of amnesia or sporadic dementia of the Alzheimer type, induced by scopolamine (SCO 1 mg/kg) and streptozotocin (STZ 3 mg/kg), respectively. In the SCO model, the animals received the Rubus sp. intragastrically at concentrations of 100 and 200 mg/kg for 10 days. In the STZ protocol, the animals received an intracerebroventricular injection of STZ and the animals were treated with blackberry extract (100 and 200 mg/kg) for 21 days. At the end of each experimental protocol, behavioral tests were performed to assess memory and after, the animals were euthanized and the cerebral cortex, hippocampus and cerebellum were collected for biochemical analysis. In the SCO protocol, donepezil was used as a positive control and in the STZ protocol, metformin was used as a positive control. In both protocols, the Rubus sp. was able to prevent or reverse memory deficits, oxidative stress and increased acetylcholinesterase (AChE) activity. In the SCO protocol, it was observed that the Rubus sp. has similar effect to donepezil. In the STZ protocol, the Rubus sp. it also prevented the increase of interleukin 6 (IL-6) in the hippocampus, and the changes in the gene expression of GSK3β and Nrf2 induced by STZ. Metformin, used in the STZ protocol, had similar effects to the Rubus sp. The obtained results highlight that the extract of Rubus sp. acts on several brain targets, thus demonstrating its neuroprotective potential and highlighting the importance of investigating natural products in diseases that affect the central nervous system (CNS).