Treatment with Blackberry Extract and Metformin in Sporadic Alzheimer's Disease Model: Impact on Memory, Inflammation, Redox Status, Phosphorylated Tau Protein and Insulin Signaling

Natural products offer promising potential for the development of new therapies for Alzheimer's disease (AD). Blackberry fruits are rich in phytochemical compounds capable of modulating pathways involved in neuroprotection. Additionally, drug repurposing and repositioning could also accelerate the development of news treatments for AD. In light of the reduced brain glucose metabolism in AD, an alternative approach has been the use of the drug metformin. Thus, the aim of this study was to evaluate the effect of treatment with blackberry extract in a model of AD induced by streptozotocin (STZ) and compare it with metformin treatment. Male rats were divided into groups: I - Control; II - STZ; III - STZ + blackberry extract (100 mg/kg); IV - STZ + blackberry extract (200 mg/kg) and V - STZ + metformin (150 mg/kg). The animals received intracerebroventricular injection of STZ or buffer. Seven days after the surgical procedure, the animals were treated orally with blackberry extract or metformin for 21 days. Blackberry extract and metformin prevented the memory impairment induced by STZ. In animals of group II, an increase in acetylcholinesterase activity, phosphorylated tau protein, IL-6, oxidative damage, and gene expression of GSK-3β and Nrf2 was observed in the hippocampus. STZ induced a decrease in IL-10 levels and down-regulated the gene expression of Akt1, IRS-1 and FOXO3a. Blackberry extract and metformin prevented the alterations in acetylcholinesterase activity, IL-6, GSK3β, Nrf2, and oxidative damage. In conclusion, blackberry extract exhibits multi-target actions in a model of AD, suggesting new therapeutic potentials for this neurodegenerative disease.