Grape Extract Protects Mitochondria from Oxidative Damage and Improves Locomotor Dysfunction and Extends Lifespan in a Drosophila Parkinson's Disease Model

Abstract

A botanical extract (Regrapex-R) prepared from whole grape (Vitis vinifera) and Polygonum cuspidatum, which contains polyphenols, including flavans, anthocyanins, emodin, and resveratrol, exhibited dose-dependent scavenging effects on reactive oxygen species (ROS). The extract inhibited increases of ROS and protein carbonyl in isolated rat liver mitochondria following exposure to 2,2'-azobis (2-amidino propane) dihydrocholoride (AAPH), a potent lipid oxidant generator. The antioxidant effects of this extract were further demonstrated by protecting enzyme activities of the mitochondrial respiratory electron transport chain (complexes I and II) and pyruvate dehydrogenase in isolated liver mitochondria with AAPH insult. In human neuroblastoma cells (SKN-MC), pretreatment of extract protected cells against AAPH induced oxidation in maintaining cell viability and inhibiting excessive ROS generation. Extract was fed to transgenic Drosophila expressing human alpha-synuclein. This model for Parkinson disease recapitulates essential features of the disorder, including loss of dopaminergic neurons in the substantia nigra and a locomotor dysfunction that is displayed by a progressive loss of climbing ability measured using a geotaxis assay. Male transgenic flies fed the extract (0.16-0.64 mg/100 g of culture medium) showed a significant improvement in climbing ability compared to controls. Female transgenic flies showed a significant extension in average lifespan. These results suggest that Regrapex-R is a potent free radical scavenger, a mitochondrial protector, and a candidate for further studies to assess its ability to protect against neurodegenerative disease and potentially extend lifespan.

A Blueberry Extract Supplemented Diet Partially Restores <i>α-Synuclein</i>-Dependent Lifespan Loss and Developmental Defects in Drosophila

“…Previous findings have demonstrated that grape extract improved both the early mortality and premature decline in locomotion in a similar Drosophila model of PD [9]. Taken together, these results epitomize the value of using Drosophila to study PD aetiology.…”

“…The therapeutic potential of blueberries in cancer and vascular disease has been described and recent studies in Drosophila suggest that plant extracts may be beneficial to individuals suffering from neurodegenerative diseases [9] [10]. In this study we describe the restorative effects of blueberry extract (BBE) concentrate on a Drosophila model of PD.…”

Oxidant effects and toxicity ofCroton campestrisinDrosophila melanogaster

“…Evidence from in vitro and in vivo studies indicate that phytochemicals such as flavonoids, proanthocyanidins and anthocyanins (Long et al 2009;Dong et al 2012;Lopez et al 2014) can improve lifespan and delay the aging process. Besides the beneficial effects of plant preparations traditionally used by human population, double-sided properties of plant extracts have been verified.…”

Effect of Resveratrol as Caloric Restriction Mimetic and Environmental Enrichment on Neurobehavioural Responses in Young Healthy Mice

“…This is contrary to the findings of Anandhan et al [37] who reported that resveratrol improves motor endurance using hang test in MPTP challenged mice. Both resveratrol and environmental enrichment have also been reported to extend lifespan and improve motor function in drosophila and rat models of Parkinson's disease, respectively, by activating sirtuins gene [15,38]. Caloric restriction and EE have been found to attenuate age-related deficits in learning and memory [15,39] and increase resistance of neurons to excitotoxic, oxidative, and metabolic insults and improve behavioural outcomes in experimental models of Alzheimer's and Huntington's disease [40].…”