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.

The generation of free radicals is a physiological event resulting mainly from the cellular respiration process and the overactivation of the NOX leads to an excess production of ROS that is associated with oxidative stress. Chrysobalanus icaco, a medicinal plant that belongs to the Chrysobalanaceae family, possesses a high number of polyphenols, including phenolic acids and flavonoids. Due to its phytochemical composition, this study aimed to evaluate the antioxidant potential of the hydroalcoholic extract from the leaves of Chrysobalanus icaco (HECi) and the inhibitory potential of its main flavonoids against NOX. The in silico predictions of absorption, distribution, metabolism, excretion, and toxicity (ADMET), drug-likeness properties, and molecular docking with the enzyme NOX (PDB code 2CDU) were also performed to support the experimental results. The phytochemical screening of the HECi showed the presence of phenols and flavonoids. HECi performed an excellent antioxidant activity (IC50 = 8.1 μg/mL), probably due to its rich phenolic (220.11 ± 0.4 mg GAE/g) and flavonoid (110.98 ± 0.37 mg QE/g) constitution. The ADMET prediction indicated that myricetin and quercetin had the best pharmacokinetic parameters. The molecular docking results showed that myricetin and especially quercetin had strong docking score on NOX (ΔG = –8.1 kcal/mol and ΔG = –8.3 kcal/mol, respectively). Frontier Orbital’s analyzes (HOMO and LUMO) suggested that quercetin has better antioxidant properties than myricetin. Our results demonstrate for the first time the in silico action of quercetin against NOX, as well as reiterate the antioxidant potential of C. icaco.

O câncer está entre as principais causas de morte no mundo. Disfunções mitocondriais – relacionadas a mutação ou não –, estresse oxidativo e ativação de células imunes se relacionam à fisiopatologia do câncer, em função da indução por múltiplas vias de fatores oncogênicos. Até o momento, a produção e o desenvolvimento de drogas antitumorais para o tratamento do câncer ainda se configura como uma barreira, até que a formulação esteja disponível em condições seguras aos pacientes. Nesse contexto, a abordagem com plantas de uso tradicional relatado, como a Ayapana triplinervis passou a chamar a atenção tendo a vista o grande potencial observado de seus metabólitos secundários e o uso amplamente difundido. Fitosteróis e flavonóides são amplamente consumidos como nutracêuticos e possuem ações antioxidantes e anti-inflamatórias relatadas. Assim, a presente revisão integrativa objetivou reunir os mecanismos pelos quais compostos anteriormente identificados em A. triplinervis desempenham atividade antitumoral, além disso, buscou-se apresentar aspectos toxicológicos atribuídos a essas moléculas. A partir da análise crítica da literatura selecionada, a presente revisão reúne dados que evidenciam que os metabólitos β-sitosterol, estigmasterol e kaempferol desempenham significativo papel antitumoral por meio de disfunção mitocondrial, rotas oxidativas e modulação gênica. Quanto aos aspectos toxicológicos dessas moléculas, o presente estudo chama atenção para a necessidade de delineamentos experimentais em modelos in vivo, haja vista a necessidade da realização de cálculos assertivos de doses efetivas – para atividade antitumoral – e tóxicas desses compostos.