Dataset Information

Suppression of Presymptomatic Oxidative Stress and Inflammation in Neurodegeneration by Grape-Derived Polyphenols.

ABSTRACT: Neurodegenerative disorders constitute a group of multifaceted conditions characterized by the progressive loss of neurons and synaptic connections consequent to a combination of specific genetic predispositions and stochastic stressors. The neuropathologies observed in both Alzheimer's and Parkinson's disease are in part attributed to compounding intrinsic and extrinsic environmental stressors, which we propose may be limited by the administration of specific grape derived phytochemicals and their metabolized derivatives, specifically polyphenols isolated from grape botanicals. Current therapies for neurodegenerative disorders are limited as they solely target the final disease pathologies including behavioral changes, cognitive deficits, proteinopathies and neuronal loss; however, this strategy is not a sustainable approach toward managing disease onset or progression. This review discusses the application of grape derived polyphenols as an adjunctive treatment paradigm for the prevention of neuropathologies associated with Alzheimer's disease, Parkinson's disease and Chronic Traumatic Encephalopathy by simultaneously ameliorating two stochastic stressors that facilitate their disease pathologies: inflammation and oxidative stress. The biophysical attributes of grape-derived polyphenols buffer against redox potential dependent peripheral and neuroinflammation and down regulate the activation of inflammasomes in microglia and astrocytes, which could provide a novel mechanism through which grape-derived polyphenols simultaneously suppress risk factors across pathologically distinct neurodegenerative conditions. This approach therefore offers a prophylactic mode, not feasible through current pharmacological agents, to target activity dependent risk factors for neurodegenerative disorders that manifest over an individual's lifetime.

SUBMITTER: Herman F

PROVIDER: S-EPMC6122113 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Suppression of Presymptomatic Oxidative Stress and Inflammation in Neurodegeneration by Grape-Derived Polyphenols.

Herman Francis F Westfall Susan S Brathwaite Justin J Pasinetti Giulio M GM

Frontiers in pharmacology 20180828

Neurodegenerative disorders constitute a group of multifaceted conditions characterized by the progressive loss of neurons and synaptic connections consequent to a combination of specific genetic predispositions and stochastic stressors. The neuropathologies observed in both Alzheimer's and Parkinson's disease are in part attributed to compounding intrinsic and extrinsic environmental stressors, which we propose may be limited by the administration of specific grape derived phytochemicals and th ...[more]

PMID: 30210334

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Project description:BACKGROUND:Chronic respiratory diseases, whose one of the hallmarks is oxidative stress, are still incurable and need novel therapeutic tools and pharmaceutical agents. The phenolic compounds contained in grape are endowed with well-recognized anti-oxidant, anti-inflammatory, anti-cancer, and anti-aging activities. Considering that natural anti-oxidants, such as proanthocyanidins, have poor water solubility and oral bioavailability, we have developed a drug delivery system based on solid lipid nanoparticles (SLN), apt to encapsulate grape seed extract (GSE), containing proanthocyanidins. METHODS:Plain, 6-coumarin (6-Coum), DiR- and GSE-loaded SLN were produced with the melt-emulsion method. Physicochemical characterization of all prepared SLN was determined by photon correlation spectroscopy and laser Doppler anemometry. MTT assay (spectrophotometry) and propidium iodide (PI) assay (cytofluorimetry) were used to assess cell viability. Flow cytometry coupled with cell imaging was performed for assessing apoptosis and necrosis by Annexin V/7-AAD staining (plain SLE), cell internalization (6-Coum-SLN) and reactive oxygen species (ROS) production (SLN-GSE). NF-κB nuclear translocation was studied by immunofluorescence. In vivo bio-imaging was used to assess lung deposition and persistence of aerosolized DiR-loaded SLN. RESULTS:Plain SLN were not cytotoxic when incubated with H441 airway epithelial cells, as judged by both PI and MTT assays as well as by apoptosis/necrosis evaluation. 6-Coum-loaded SLN were taken up by H441 cells in a dose-dependent fashion and persisted into cells at detectable levels up to 16 days. SLN were detected in mice lungs up to 6 days. SLN-GSE possessed 243 nm as mean diameter, were negatively charged, and stable in size at 37 °C in Simulated Lung Fluid up to 48 h and at 4 °C in double distilled water up to 2 months. The content of SLN in proanthocyanidins remained unvaried up to 2 months. GSE-loaded SLN determined a significant reduction in ROS production when added 24-72 h before the stimulation with hydrogen peroxide. Interestingly, while at 24 h free GSE determined a higher decrease of ROS production than SLN-GSE, the contrary was seen at 48 and 72 h. Similar results were observed for NF-κB nuclear translocation. CONCLUSIONS:SLN are a biocompatible drug delivery system for natural anti-oxidants obtained from grape seed in a model of oxidative stress in airway epithelial cells. They feature stability and long-term persistence inside cells where they release proanthocyanidins. These results could pave the way to novel anti-oxidant and anti-inflammatory therapies for chronic respiratory diseases.

Dataset Information

Suppression of Presymptomatic Oxidative Stress and Inflammation in Neurodegeneration by Grape-Derived Polyphenols.

Publications

Suppression of Presymptomatic Oxidative Stress and Inflammation in Neurodegeneration by Grape-Derived Polyphenols.

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