Alzheimer’s disease (AD) is a progressive and neurodegenerative disorder of the cortex and hippocampus, which eventually leads to cognitive impairment. Although the etiology of AD remains unclear, the presence of β‐amyloid (Aβ) peptides in these learning and memory regions is a hallmark of AD. Therefore, the inhibition of Aβ peptide aggregation has been considered the primary therapeutic strategy for AD treatment. Many studies have shown that resveratrol has antioxidant, anti‐inflammatory, and neuroprotective properties and can decrease the toxicity and aggregation of Aβ peptides in the hippocampus of AD patients, promote neurogenesis, and prevent hippocampal damage. In addition, the antioxidant activity of resveratrol plays an important role in neuronal differentiation through the activation of silent information regulator‐1 (SIRT1). SIRT1 plays a vital role in the growth and differentiation of neurons and prevents the apoptotic death of these neurons by deacetylating and repressing p53 activity; however, the exact mechanisms remain unclear. Resveratrol also has anti‐inflammatory effects as it suppresses M1 microglia activation, which is involved in the initiation of neurodegeneration, and promotes Th2 responses by increasing anti‐inflammatory cytokines and SIRT1 expression. This review will focus on the antioxidant and anti‐inflammatory neuroprotective effects of resveratrol, specifically on its role in SIRT1 and the association with AD pathophysiology.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by impairments in the cognitive domains associated with orientation, recording, and memory. This pathology results from an abnormal deposition of the β-amyloid (Aβ) peptide and the intracellular accumulation of neurofibrillary tangles. Mitochondrial dysfunctions play an important role in the pathogenesis of AD, due to disturbances in the bioenergetic properties of cells. To date, the usual therapeutic drugs are limited because of the diversity of cellular routes in AD and the toxic potential of these agents. In this context, alpha-lipoic acid (α-LA) is a well-known fatty acid used as a supplement in several health conditions and diseases, such as periphery neuropathies and neurodegenerative disorders. It is produced in several cell types, eukaryotes, and prokaryotes, showing antioxidant and anti-inflammatory properties. α-LA acts as an enzymatic cofactor able to regulate metabolism, energy production, and mitochondrial biogenesis. In addition, the antioxidant capacity of α-LA is associated with two thiol groups that can be oxidised or reduced, prevent excess free radical formation, and act on improvement of mitochondrial performance. Moreover, α-LA has mechanisms of epigenetic regulation in genes related to the expression of various inflammatory mediators, such PGE2, COX-2, iNOS, TNF-α, IL-1β, and IL-6. Regarding the pharmacokinetic profile, α-LA has rapid uptake and low bioavailability and the metabolism is primarily hepatic. However, α-LA has low risk in prolonged use, although its therapeutic potential, interactions with other substances, and adverse reactions have not been well established in clinical trials with populations at higher risk for diseases of aging. Thus, this review aimed to describe the pharmacokinetic profile, bioavailability, therapeutic efficacy, safety, and effects of combined use with centrally acting drugs, as well as report in vitro and in vivo studies that demonstrate the mitochondrial mechanisms of α-LA involved in AD protection.

Piceatannol is a resveratrol metabolite that is considered a potent antioxidant and cytoprotector because of its high capacity to chelate/sequester reactive oxygen species. In pathogenesis of periodontal diseases, the imbalance of reactive oxygen species is closely related to the disorder in the cells and may cause changes in cellular metabolism and mitochondrial activity, which is implicated in oxidative stress status or even in cell death. In this way, this study aimed to evaluate piceatannol as cytoprotector in culture of human periodontal ligament fibroblasts through in vitro analyses of cell viability and oxidative stress parameters after oxidative stress induced as an injury simulator. Fibroblasts were seeded and divided into the following study groups: control, vehicle, control piceatannol, H₂O₂ exposure, and H₂O₂ exposure combined with the maintenance in piceatannol ranging from 0.1 to 20 μM. The parameters analyzed following exposure were cell viability by trypan blue exclusion test, general metabolism status by the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method, mitochondrial activity through the ATP production, total antioxidant capacity, and reduced gluthatione. Piceatannol was shown to be cytoprotective due the maintenance of cell viability between 1 and 10 μM even in the presence of H₂O₂. In a concentration of 0.1 μM piceatannol decreased significantly cell viability but increased cellular metabolism and antioxidant capacity of the fibroblasts. On the other hand, the fibroblasts treated with piceatannol at 1 μM presented low metabolism and antioxidant capacity. However, piceatannol did not protect cells from mitochondrial damage as measured by ATP production. In summary, piceatannol is a potent antioxidant in low concentrations with cytoprotective capacity, but it does not prevent all damage caused by hydrogen peroxide.

Ethanol (EtOH) binge drinking is characterized by high EtOH intake during few hours followed by withdrawal. Protection strategies against the damages generated by this binge are poorly explored. Thus, this study is aimed at investigating the protective role of treadmill physical exercise (PE) on the damage caused after repeated cycles of binge-like EtOH exposure in the oxidative biochemistry, morphology, and cerebellar function of rats from adolescence to adulthood. For this, animals were divided into four groups: control group (sedentary animals with doses of distilled water), exercised group (exercised animals with doses of distilled water), EtOH group (sedentary animals with doses of 3 g/kg/day of EtOH, 20% w/v), and exercised+EtOH group (exercised animals with previous mentioned doses of EtOH). The PE occurred on a running treadmill for 5 days a week for 4 weeks, and all doses of EtOH were administered through intragastric gavage in four repeated cycles of EtOH in a binge-like manner. After the EtOH protocol and PE, animals were submitted to open field and beam walking tests. In sequence, the cerebellums were collected for the biochemical and morphological analyses. Biochemical changes were analyzed by measurement of Trolox equivalent antioxidant capacity (TEAC), reduced glutathione content measurements (GSH), and measurement of nitrite and lipid peroxidation (LPO). In morphological analyses, Purkinje cell density evaluation and immunohistochemistry evaluation were measured by antimyelin basic protein (MBP) and antisynaptophysin (SYP). The present findings demonstrate that the binge drinking protocol induced oxidative biochemistry misbalance, from the decrease of TEAC levels and higher LPO related to tissue damage and motor impairment. In addition, we have shown for the first time that treadmill physical exercise reduced tissue and functional alterations displayed by EtOH exposure.

The heavy and episodic EtOH drinking pattern, equivalent to weekend consumption, characterizes the binge-drinking pattern and promotes a misbalance of encephalic metabolic functions, concurring to neurodegeneration and cerebral dysfunction. And for being a legal drug, it has global public health and social relevance. In this way, we aimed to investigate the effects of physical training, in a treadmill, on the deleterious effects of EtOH on hippocampal functions, related to memory and learning. For this, we used 40 Wistar rats, divided into four groups: Control group, Trained group (trained animals with doses of distilled water), EtOH group (nontrained animals with doses of 3 g/kg/day of EtOH, 20% w/v), and Trained+EtOH group (trained animals exposed to EtOH). The physical exercise was performed by running on a treadmill for 5 days a week for 4 weeks, and all doses of EtOH were administered through intragastric gavage in four repeated cycles of EtOH in binge. After the experimental period, the animals were submitted to the object recognition task and Morris water maze test, and after being euthanized, the blood and hippocampus were collected for Trolox Equivalent Antioxidant Capacity (TEAC), Reduced Glutathione Content (GSH), and Nitrite and Lipid Peroxidation (LPO) level measurements. Our results showed that EtOH caused marked oxidative stress and mnemonic damage, and the physical exercise promoted neuroprotective effects, among them, the modulation of oxidative biochemistry in plasma (by restoring GSH levels) and in the hippocampus (by reducing LPO levels and increasing antioxidant parameters) and cognitive function improvement. Therefore, physical exercise can be an important prophylactic and therapeutic tool in order to ameliorate and even prevent the deleterious effects of EtOH on cognitive functions.

Recent evidence suggests that replacing saturated fat with unsaturated fat is beneficial for cardiovascular health. This study compared the effects of Brazil nut oil (BNO) and soybean oil (SO) supplementation for 30 days on anthropometric, blood pressure, biochemical, and oxidative parameters in patients with metabolic syndrome (MS). Thirty-one patients with MS were randomly allocated to receive 30 sachets with 10 mL each of either BNO (n = 15) or SO (n = 16) for daily supplementation. Variables were measured at the beginning of the study and after 30 days of intervention. No change in anthropometric and blood pressure variables were observed (p > 0.05). Total (p = 0.0253) and low-density lipoprotein (p = 0.0437) cholesterol increased in the SO group. High-density lipoprotein cholesterol decreased (p = 0.0087) and triglycerides increased (p = 0.0045) in the BNO group. Malondialdehyde levels decreased in the BNO group (p = 0.0296) and total antioxidant capacity improved in the SO group (p = 0.0110). Although the addition of oils without lifestyle interventions did not affect anthropometric findings or blood pressure and promoted undesirable results in the lipid profile in both groups, daily supplementation of BNO for 30 days decreased lipid peroxidation, contributing to oxidative stress reduction.