Efeito neuroprotetor do vinho ruby cabernet sobre o prejuízo de memória em camundongos hipercolesterolêmicos

Abstract

Hypercholesterolemia is characterized by the pathological elevation of the blood cholesterol level, increasing the formation of free radicals, which causes oxidation and damage to the cellular lipids causing inflammatory activity growth and negative progression of cognitive function. Red wine consumption minimizes these effects by inhibiting cytokine expression and modulating levels of brain-derived neurotrophic factor (BDNF), cyclic cAMP-binding element (CREB), microRNAs (miRNA), and the action of the enzyme acetylcholinesterase (AChE). Antioxidants, flavonoids and polyphenols have become the first substances contained in red wine with proven beneficial effects in various diseases, such as the inhibition of LDL oxidation and parameters involved in the inflammatory response. Regular ingestion of polyphenol-rich beverages has a positive effect on human health, such as reducing the incidence of cardiovascular diseases, cancer and protection against neurodegenerative diseases, among others. Therefore, the present study aimed to investigate the potential neuroprotective effect of Ruby Carbenet wine in knockout mice for the Ldlr-/- receptor exposed to the hypercholesterolemic diet. The wine was submitted to in vitro analysis for quantification of polyphenols, anthocyanins, caffeic acid, gallic acid, epicatechin and resveratrol. 40 adult mice with 90 days, from 20 to 25 grams were used. The animals were divided into 4 groups (n=10) and for the induction of hypercholesterolemia cholesterol was diluted in pure alcohol 96 ° C, on the commercial diet (Puro Trato PB 22) for 90 days. At the end of the treatment was performed memory behavioral test, Morris water maze task (MWMT), soon after, blood was collected by cardiac puncture and the prefrontal cortex and hippocampus were removed for biochemical assays. The levels of plasma lipids and proinflammatory cytokines, interferon gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the hippocampus and prefrontal cortex. We also evaluated the activity of AChE and the levels of the structural proteins BDNF and CREB, and the biomarkers microRNAs. Our results showed that the hypercholesterolemic diet causes an increase in plasma lipids, proinflammatory cytokines and AChE enzyme activity in Ldlr-/- mice, which was attenuated by the consumption of red wine through the reduction of the inflammatory state. The high cholesterol diet decreased levels of BDNF, CREB and brain microRNAs, and moderate consumption of red wine was able to revert these structural proteins BDNF and CREB, and the miRNA146a and 155 biomarkers, promoting neuroprotection and the improvement of memory. Ruby Cabernet wine showed antioxidant potential confirmed by its content of gallic acid 135.3 mg/L, caffeic acid 91.2 mg/L, epicatechin 242.2 mg/L and resveratrol 102.2 mg/L. The moderate consumption of wine gave the mice an improvement in cognitive deficit and plasticity, corroborating with the result of the behavioral test, in which MWMT is related to the learning and memory system. Thus, it was verified that Ruby Carbenet wine demonstrated neuroprotective effect and reduced plasma lipid levels, modulating cytokines, acting to maintain neuroplasticity and regulate acetylcholinesterase activity in hypercholesterolemic mice. Keywords: Phenolic compounds. Cognitive deficit. Diet with high cholesterol. Knockout mice for Ldlr-/- receptor. Neuroplasticity.