Neurodegenerative diseases are characterized by the progressive loss of neurons in different regions of the nervous system. Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most prevalent neurodegenerative diseases, and the symptoms associated with these pathologies are closely related to the regions that are most affected by the process of neurodegeneration. Despite their high prevalence, currently, there is no cure or disease-modifying drugs for the treatment of these conditions. In the last decades, due to the need for the development of new treatments for neurodegenerative diseases, several authors have investigated the neuroprotective actions of naturally occurring molecules, such as resveratrol. Resveratrol is a stilbene found in several plants, including grapes, blueberries, raspberries, and peanuts. Studies have shown that resveratrol presents neuroprotective actions in experimental models of AD and PD, however, its clinical application is limited due to its rapid metabolism and low bioavailability. In this context, studies have proposed that structural changes in the resveratrol molecule, including glycosylation, alkylation, halogenation, hydroxylation, methylation, and prenylation could lead to the development of derivatives with enhanced bioavailability and pharmacological activity. Therefore, this review article aims to discuss how resveratrol derivatives could represent viable molecules in the search for new drugs for the treatment of AD and PD.
Polydatin, or piceid, is a natural stilbene found in grapes, peanuts, and wines. Polydatin presents pharmacological activities, including neuroprotective properties, exerting preventive and/or therapeutic effects in central nervous system (CNS) disorders. In the present study, we summarize and discuss the neuroprotective effects of polydatin in CNS disorders and related pathological conditions in preclinical animal studies. A systematic review was performed by searching online databases, returning a total of 110 records, where 27 articles were selected and discussed here. The included studies showed neuroprotective effects of polydatin in experimental models of neurological disorders, including cerebrovascular disorders, Parkinson's disease, traumatic brain injuries, diabetic neuropathy, glioblastoma, and neurotoxicity induced by chemical agents. Most studies were focused on stroke (22.2%) and conducted in male rodents. The intervention protocol with polydatin was mainly acute (66.7%), with postdamage induction treatment being the most commonly used regimen (55.2%). Overall, polydatin ameliorated behavioral dysfunctions and/or promoted neurological function by virtue of its antioxidant and antiinflammatory properties. In summary, this review offers important scientific evidence for the neuroprotective effects and distinct pharmacological mechanisms of polydatin that not only enhances the present understanding but is also useful for the development of future preclinical and clinical investigations.
Permethrin (PM) is a synthetic pyrethroid insecticide widely used as domestic repellent. Damage effects to nontarget organisms have been reported, particularly in the early stages of development. Studies indicate redox unbalance as secondary PM effect. Therefore, our goal was to investigate the acute PM effects on larval zebrafish. Larvae (6 days postfertilization) were exposed to PM (25–600 μg/L) during 24 hours, and 50% lethal concentration was estimated. For subsequent assays, the sublethal PM concentrations of 25 and 50 μg/L were used. PM increased anxiety-like behaviors according to the Novel Tank and Light-Dark tests. At the molecular level, PM induced increased ROS, which may be related to the increased lipid peroxidation, DNA damage, and apoptosis detected in PM-exposed organisms. In parallel, upregulation of the antioxidant system was detected after PM exposure, with increased superoxide dismutase, glutathione S-transferase and glutathione reductase activities, and thiol levels. The increased of Nrf2 target genes and the activation of an electrophile response element-driven reporter Tg(EPRE:LUC-EGFP) suggest that the Nrf2 pathway can mediate a fast response to PM, leading to antioxidant amplification. By using high-resolution respirometry, we found that exposure to PM decreased the oxygen consumption in all respiratory stages, disrupting the oxidative phosphorylation and inhibiting the electron transfer system, leading to decrease in bioenergetics capacity. In addition, PM led to increases of residual oxygen consumption and changes in substrate control ratio. Glucose metabolism seems to be affected by PM, with increased lactate dehydrogenase and decreased citrate synthase activities. Taken together, our results demonstrated the adverse effects of acute sublethal PM concentrations during larval development in zebrafish, causing apparent mitochondrial dysfunction, indicating a potential mechanism to redox unbalance and oxidative stress, which may be linked to the detected cell death and alterations in normal behavior patterns caused by acute PM exposure.
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