O flavonóide Eriodictiol protege camundongos com Doença de Alzheimer Esporádica induzida por Estreptozotocina: estudo in vivo e in silico

Abstract

Alzheimer's Disease (AD) is a neurodegenerative disorder that causes progressive memory lossand other cognitive impairments, being the most common form of dementia and affecting 48.6million people worldwide. However, recent research suggests that Sporadic Alzheimer'sDisease (SAD) is a Type 3 Diabetes, characterized by insulin resistance in the brain, involvingmolecular mechanisms similar to those causing Type 2 Diabetes in peripheral tissue. Thus,intracerebroventricular (icv) injections of streptozotocin (STZ) have been used as a model ofType 3 diabetes induction and as an experimental model of SAD due to causing oxidative stressand inflammation. This work aimed to study the effects of eriodictyol, a flavonoid with alreadydescribed anti-inflammatory and antioxidant activity, on cognitive deficits and neuronaldamage in mice subjected to the experimental model of SAD. Male Swiss mice (25-35 g)received bilateral STZ injections (3 mg/kg, icv, 1.5 μl) on day 1 and 3 of the experiment andwere divided into 5 groups: Control; Control + eriodictyol 4 (ERI 4); STZ; STZ + ERI (2 and4 mg/kg). Eriodictyol treatment was carried out for 16 days, starting 1 hour after the secondinduction procedure. Blood glucose measurement of the animals was performed before andafter the induction of SAD. The results showed that there was no significant change in bloodglucose. The treatment significantly improved the deficits in aversive, recognition and spatialmemory and did not alter locomotor activity. The neuroprotective effect is probably due to anantioxidant and anti-inflammatory action via inactivation of GSK-3β and activation of theKeap1/Nrf2 pathway, highlighted in the in silico experiments, which prevented the reductionof GSH levels and decreased nitrite levels in the hippocampus of the animals, thus attenuatingthe neuroinflammatory process and insulin resistance, highlighting its potential for preventiveand/or adjuvant treatment of SAD.