茶多酚在帕金森病中的神经保护作用研究进展

帕金森病(Parkinson’s disease,PD)是一种常见的神经退行性疾病.茶叶中特有的多酚类物质在预防神经退行性疾病方面具有重要作用.大量的体外研究表明,茶多酚在PD中通过抗氧化、铁螯合、抑制α-突触核蛋白聚集和调节细胞内信号通路等机制发挥神经保护作用.综述了茶多酚在PD模型动物和临床研究中的神经保护作用,对今后茶多酚在抗PD的研究中存在的问题和发展趋势给出了建议.     

阿尔茨海默症病理机制中的金属代谢和金属药物

随着人口老龄化进程的发展,阿尔茨海默症(AD)已成为威胁中国和世界人口健康和经济的重大疾病.本文综述了近年来AD病理的分子机制的新进展,分析了其中金属代谢的意义.研究发现,在AD进程中,围绕淀粉样斑块(AP)和神经缠绕斑(NFT)的形成,多因素相互联系并发挥作用,这些主要因素包括金属内稳态、胰岛素抵抗、神经炎症、线粒体和血脑屏障改变等.与AD病理过程密切相关的主要蛋白质均参与了金属元素的生理代谢过程,而细胞金属离子的内稳态失衡加剧了AD病理的恶化.金属药物在AD诊断和治疗中可能具有以下的发展潜力:(1)AD早期诊断探针;(2)调节金属内稳态的配体和/或微量元素补充;(3)抗糖尿病金属配合物;(4)神经元和血脑屏障(BBB)保护金属药物.     

Neuroprotection of N-benzyl Eicosapentaenamide in Neonatal Mice Following Hypoxic–Ischemic Brain Injury

Maca (Lepidium meyenii) has emerged as a popular functional plant food because of its medicinal properties and nutritional value. Macamides, as the exclusively active ingredients found in maca, are a unique series of non-polar, long-chain fatty acid N-benzylamides with multiple bioactivities such as antifatigue characteristics and improving reproductive health. In this study, a new kind of macamide, N-benzyl eicosapentaenamide (NB-EPA), was identified from maca. We further explore its potential neuroprotective role in hypoxic–ischemic brain injury. Our findings indicated that treatment with biosynthesized NB-EPA significantly alleviates the size of cerebral infarction and improves neurobehavioral disorders after hypoxic–ischemic brain damage in neonatal mice. NB-EPA inhibited the apoptosis of neuronal cells after ischemic challenge. NB-EPA improved neuronal cell survival and proliferation through the activation of phosphorylated AKT signaling. Of note, the protective property of NB-EPA against ischemic neuronal damage was dependent on suppression of the p53–PUMA pathway. Taken together, these findings suggest that NB-EPA may represent a new neuroprotectant for newborns with hypoxic–ischemic encephalopathy.     

Effect of Water and Ethanol Extracts from Hericium erinaceus Solid-State Fermented Wheat Product on the Protection and Repair of Brain Cells in Zebrafish Embryos

Extracts from Hericium erinaceus can cause neural cells to produce nerve growth factor (NGF) and protect against neuron death. The objective of this study was to evaluate the effects of ethanol and hot water extracts from H. erinaceus solid-state fermented wheat product on the brain cells of zebrafish embryos in both pre-dosing protection mode and post-dosing repair mode. The results showed that 1% ethanol could effectively promote zebrafish embryo brain cell death. Both 200 ppm of ethanol and water extracts from H. erinaceus solid-state fermented wheat product protected brain cells and significantly reduced the death of brain cells caused by 1% ethanol treatment in zebrafish. Moreover, the zebrafish embryos were immersed in 1% ethanol for 4 h to cause brain cell damage and were then transferred and soaked in the 200 ppm of ethanol and water extracts from H. erinaceus solid-state fermented wheat product to restore the brain cells damaged by the 1% ethanol. However, the 200 ppm extracts from the unfermented wheat medium had no protective and repairing effects. Moreover, 200 ppm of ethanol and water extracts from H. erinaceus fruiting body had less significant protective and restorative effects on the brain cells of zebrafish embryos. Both the ethanol and hot water extracts from H. erinaceus solid-state fermented wheat product could protect and repair the brain cells of zebrafish embryos damaged by 1% ethanol. Therefore, it has great potential as a raw material for neuroprotective health product.     

Effects of Grape Polyphenols on the Life Span and Neuroinflammatory Alterations Related to Neurodegenerative Parkinson Disease-Like Disturbances in Mice

Functional nutrition is a valuable supplementation to dietary therapy. Functional foods are enriched with biologically active substances. Plant polyphenols attract particular attention due to multiple beneficial properties attributed to their high antioxidant and other biological activities. We assessed the effect of grape polyphenols on the life span of C57BL/6 mice and on behavioral and neuroinflammatory alterations in a transgenic mouse model of Parkinson disease (PD) with overexpression of the A53T-mutant human α-synuclein. C57BL/6 mice were given a dietary supplement containing grape polyphenol concentrate (GPC—1.5 mL/kg/day) with drinking water from the age of 6–8 weeks for life. Transgenic PD mice received GPC beginning at the age of 10 weeks for four months. GPC significantly influenced the cumulative proportion of surviving and substantially augmented the average life span in mice. In the transgenic PD model, the grape polyphenol (GP) diet enhanced memory reconsolidation and diminished memory extinction in a passive avoidance test. Behavioral effects of GP treatment were accompanied by a decrease in α-synuclein accumulation in the frontal cortex and a reduction in the expression of neuroinflammatory markers (IBA1 and CD54) in the frontal cortex and hippocampus. Thus, a GP-rich diet is recommended as promising functional nutrition for aging people and patients with neurodegenerative disorders.     

Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection

Like other organs, brain functions diminish with age. Furthermore, for a variety of neurological disorders—including Alzheimer’s disease—age is one of the higher-risk factors. Since in many Western countries the average age is increasing, determining approaches for decreasing the effects of aging on brain function is taking on a new urgency. Neuroinflammation and oxidative stress are two convoluted key factors in brain aging and chronic neurodegenerative diseases. The diverseness of factors, causing an age-related decrease in brain functions, requires identifying small molecules that have multiple biological activities that can affect all these factors. One great source of these small molecules is related to polyphenolic flavonoids. Recently, 3,3′,4′,7-tetrahydroxyflavone (fisetin) has been reported as a potent senotherapeutic capable of extending lifespan by reducing peroxidation levels and enhancing antioxidant cell responses. The neuroprotective effects of fisetin have been shown in several in vitro and in vivo models of neurological disorders due to its actions on multiple pathways associated with different neurological disorders. The present work aims to collect the most recent achievements related to the antioxidant and neuroprotective effects of fisetin. Moreover, in silico pharmacokinetics, pharmacodynamics, and toxicity of fisetin are also comprehensively described along with emerging novel drug delivery strategies for the amelioration of this flavonol bioavailability and chemical stability.     

Phenylalanine-Based AMPA Receptor Antagonist as the Anticonvulsant Agent with Neuroprotective Activity—In Vitro and In Vivo Studies

Trying to meet the multitarget-directed ligands strategy, a series of previously described aryl-substituted phenylalanine derivatives, reported as competitive antagonists of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, were screened in vitro for their free-radical scavenging and antioxidant capacity in two different assays: ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity fluorescent (ORAC-FL) assays. The most active antioxidants 1 and 8 were further examined to evaluate their neuroprotective properties in vitro. In this study, compound 1 showed a significant neuroprotective effect against the neurotoxin 6-hydroxydopamine in neuroblastoma SH-SY5Y and IMR-32 cell lines. Both compounds also showed prevention from high levels of reactive oxygen species (ROS) in SH-SY5Y cells. Furthermore, the desired monoamine oxidase B (MAO-B) inhibition effect (IC₅₀ = 278 ± 29 nM) for 1 was determined. No toxic effects up to 100 µM of 1 and 8 against neuroblastoma cells were observed. Furthermore, in vivo studies showed that compound 1 demonstrated significant anticonvulsant potential in 6-Hz test, but in neuropathic pain models its antiallodynic and antihyperalgesic properties were not observed. Concluding, the compound 1 seems to be of higher importance as a new phenylalanine-based lead candidate due to its confirmed promise in in vitro and in vivo anticonvulsant activity.