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.

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

“…The animals were perfused transcardially with phosphate-buffered saline (PBS) followed by 4% paraformaldehyde in PBS, then the brains were rapidly excised and postfixed in PBS containing 30% sucrose at 4 • C until further neuromorphological analysis. The analysis was performed on 30-µm-thick cryosections according to a protocol described in detail previously [18]. Coronal slices along the frontal cortex (AP: 2.93 to −2.45 mm) or hippocampus (AP: −2.03 to −2.15 mm) of each mouse brain were made.…”

“…In addition, polyphenols can overcome the blood-brain barrier and produce a neuroprotective effect on the central nervous system [16,17]. Hence, the application of grape-derived polyphenols as an adjunctive treatment paradigm to prevent neuropathologies including such neurodegenerative disorders as Alzheimer and Parkinson diseases is widely discussed [18]. Parkinson disease (PD) is the second most common neurodegenerative disorder, placing huge economic and social burdens on societies all over the world.…”

“…Moreover, PD patients develop drug tolerance and suffer from serious side effects of the drugs due to uninterrupted long-term treatment. Nutritional supplementation with polyphenols is regarded as a promising prophylactic treatment for neurodegenerative disorders, as it potently and simultaneously targets inflammatory and oxidative pathways [18]. It is noteworthy that a recent study by Ben Youssef et al [19] evidenced the neuroprotective effect of grape seed and skin extract on a mouse PD model induced by 6-OHDA neurotoxin through reducing apoptosis, oxidative stress, and inflammation.…”

Oxidative Stress and Nutraceuticals in the Modulation of the Immune Function: Current Knowledge in Animals of Veterinary Interest

“…Grape polyphenols are considered as potent antioxidants and several studies in human have been conducted, as it can be seen from recently published reviews [125,126]. Even if grape polyphenols can be found in commercial supplements and complete diets for companion animals, in literature no scientific publication in this field are found, while few published studies are available for ruminants [99,100,105,109,110,114].…”

1-Deoxynojirimycin in Mulberry (Morus indica L.) Leaves Ameliorates Stable Angina Pectoris in Patients With Coronary Heart Disease by Improving Antioxidant and Anti-inflammatory Capacities

“…Oxidative stress (Yan et al, 2009) and inflammatory responses (Militaru et al, 2013; Galon et al, 2015) are associated with SAP risks, whereas oxidative stress and inflammation can interact and promote each other (Herman et al, 2018; Zahran and Emam, 2018), possibly aggravating SAP. Oxidative stress and inflammation are associated with endothelial dysfunction (Zhenyukh et al, 2018), and impaired endothelial function results in blood flow decrease (Brunnekreef et al, 2012), vasospasm (Ganz et al, 1991), and embolus formation (Muci-Mendoza et al, 1980).…”