Determination of Flavonoids and Phenolic Acids in the Liver of Wistar Rats after a Dietary Enrichment with Corinthian Currant (Vitis vinifera L., var. Apyrena): A Liquid Chromatography-Tandem Mass Spectrometry Study.

Corinthian currants are dried fruits produced from Vitis vinifera L. var. Apyrena grape. This study investigated the distribution of phenolic compounds in male Wistar rat livers following two distinct Corinthian currant long-term dietary intake protocols (3 and 10% w/w). Method optimization, comparing fresh and lyophilized tissues, achieved satisfactory recoveries (>70%) for most analytes. Enzymatic hydrolysis conditions (37 °C, pH 5.0) minimally affected phenolics, but enzyme addition showed diverse effects. Hydrolyzed lyophilized liver tissue from rats consuming Corinthian currants (3 and 10% w/w) exhibited elevated levels of isorhamnetin (20.62 ± 2.27 ng/g tissue and 33.80 ± 1.38 ng/g tissue, respectively), along with similar effects for kaempferol, quercetin, and chrysin after prolonged Corinthian currant intake. This suggests their presence as phase II metabolites in the fasting-state liver. This study is the first to explore phenolic accumulation in rat liver, simulating real conditions of dried fruit consumption, as seen herein with Corinthian currant.

Brain polar phenol content, behavioural and neurochemical effects of Corinthian currant in a rotenone rat model of Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of nigral dopaminergic neurons, leading to reduced motor control. A contributing factor for the nigrostriatal degeneration is known to be oxidative stress, while antioxidant/anti-inflammatory properties of natural polyphenols have been suggested to show beneficial effects. The present study questioned the potential neuroprotective effects of supplementary diet with Corinthian currant, using a rat rotenone PD model. METHODS: The alterations in motor activity, brain Corinthian currant polar phenols' accumulation, expression patterns of tyrosine hydroxylase (TH), dopamine transporter (DAT) and brain-derived neurotrophic factor (BDNF) in the nigrostriatal dopaminergic system were determined in rotenone-treated, currant-diet rats and matching controls. RESULTS: Rotenone treatment resulted in motor deficits and TH expression decreases in the nigrostriatal pathway, exhibiting PD-like behavioural motor and neurochemical phenotypes. Interestingly, 38 days Corinthian currant consumption resulted in differential accumulation of polar phenols in mesencephalon and striatum and had a significant effect on attenuating motor deficits and dopaminergic cell loss in substantia nigra pars compacta. In addition, it induced up-regulation of BDNF expression in the nigrostriatal dopaminergic system. DISCUSSION: Taken all together, evidence is provided for the potential neuroprotective influences of Corinthian currant consumption, involving the neurotrophic factor BDNF, in rescuing aspects of PD-like phenotype.

Temporal Pattern of Neuroinflammation Associated with a Low Glycemic Index Diet in the 5xFAD Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is associated with brain amyloid-ß (Aß) peptide accumulation and neuroinflammation. Currants, a low glycemic index dried fruit, and their components display pleiotropic neuroprotective effects in AD. We examined how diet containing 5% Corinthian currant paste (CurD) administered in 1-month-old 5xFAD mice for 1, 3, and 6 months affects Aß levels and neuroinflammation in comparison to control diet (ConD) or sugar-matched diet containing 3.5% glucose/fructose (GFD). No change in serum glucose or insulin levels was observed among the three groups. CurD administered for 3 months reduced brain Aß42 levels in male mice as compared to ConD and GFD, but after 6 months, Aß42 levels were increased in mice both on CurD and GFD compared to ConD. CurD for 3 months also reduced TNFα and IL-1ß levels in male and female mouse cortex homogenates compared to ConD and GFD. However, after 6 months, TNFα levels were increased in cortex homogenates of mice both on CurD and GFD as compared to ConD. A similar pattern was observed for TNFα-expressing cells, mostly co-expressing the microglial marker CD11b, in mouse hippocampus. IL-1ß levels were similarly increased in the brain of all groups after 6 months. Furthermore, a time dependent decrease of secreted TNFα levels was found in BV2 microglial cells treated with currant phenolic extract as compared to glucose/fructose solution. Overall, our findings suggest that a short-term currant consumption reduces neuroinflammation in 5xFAD mice as compared to sugar-matched or control diet, but longer-term intake of currant or sugar-matched diet enhances neuroinflammation.

Protective Effects of Currants (Vitis vinifera) on Corticolimbic Serotoninergic Alterations and Anxiety-like Comorbidity in a Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of nigral dopaminergic neurons. Increasing evidence supports that PD is not simply a motor disorder but a systemic disease leading to motor and non-motor symptoms, including memory loss and neuropsychiatric conditions, with poor management of the non-motor deficits by the existing dopaminergic medication. Oxidative stress is considered a contributing factor for nigrostriatal degeneration, while antioxidant/anti-inflammatory properties of natural phyto-polyphenols have been suggested to have beneficial effects. The present study aimed to determine the contribution of monoaminergic neurotransmission on the anxiety-like phenotype in a rat rotenone PD model and evaluate the possible neuroprotective effects of black Corinthian currant, Vitis vinifera, consisting of antioxidant polyphenols. Rotenone-treated rats showed anxiety-like behavior and exploratory deficits, accompanied by changes in 5-HT, SERT and ß2-ARs expression in the prefrontal cortices, hippocampus and basolateral amygdala. Importantly, the motor and non-motor behavior, as well as 5-HT, SERT and ß2-ARs expression patterns of the PD-like phenotype were partially recovered by a supplementary diet with currants. Overall, our results suggest that the neuroprotective effects of Corinthian currants in rotenone-induced anxiety-like behavior may be mediated via corticolimbic serotonergic transmission.

Long lasting effects of chronic WIN55,212-2 treatment on mesostriatal dopaminergic and cannabinoid systems in the rat brain.

Cannabinoid administration modulates dopamine transmission via an indirect, multisynaptic mechanism that includes the activation of cannabinoid type-1 receptor (CB1R). The present study evaluated in rodents, the effects of acute and chronic (20 days) WIN55,212-2 administration, a non-selective CB1R agonist, on dopamine uptake and synthesis in the mesolimbic and nigrostriatal dopaminergic pathways and associate them to its effects on the endocannabinoid system. The effect of spontaneous withdrawal, after different abstinence periods (7 days, 20 days), was also assessed. Acute and chronic administration of WIN55,212-2 decreased dopamine transporter (DAT) binding and mRNA levels, as well as tyrosine hydroxylase (TH) mRNA expression in the substantia nigra (SN) and ventral tegmental area (VTA). In the striatum, chronic WIN55,212-2 administration led to decreased protein expression of DAT and TH, whereas no alterations were observed after acute administration, suggesting a diminished dopamine uptake and synthesis after chronic agonist treatment. Furthermore, after chronic agonist treatment, we observed reduced CB1R binding and mRNA levels in SN and striatum, providing evidence for a possible regulatory role of the endocannabinoid system on dopaminergic function. Seven days after WIN55,212-2 cessation, we observed a rebound increase in mRNA, binding and total protein levels of DAT and TH in VTA, SN and striatum proposing the existence of a biphasic expression pattern, which was also observed in CB1R binding levels. Within the 20-day period of abstinence, TH mRNA and protein levels and CB1R binding levels remain increased. The above results indicate that chronic CB1R agonist treatment induces long-lasting control of the mesostriatal dopaminergic activity.

Behavioral and neurochemical changes in mesostriatal dopaminergic regions of the rat after chronic administration of the cannabinoid receptor agonist WIN55,212-2.

BACKGROUND: The endocannabinoid system interacts extensively with other neurotransmitter systems and has been implicated in a variety of functions, including regulation of basal ganglia circuits and motor behavior. The present study examined the effects of repeated administration of the nonselective cannabinoid receptor 1 agonist WIN55,212-2 on locomotor activity and on binding and mRNA levels of dopamine receptors and transporters and GABAA receptors in mesostriatal dopaminergic regions of the rat. METHODS: Rats received systemic injections of WIN55,212-2 (0, 0.1, 0.3, or 1mg/kg, intraperitoneally) for 20 consecutive days. Locomotor activity was measured on days 1, 10, and 20. Following the last measurement, rats were euthanized and prepared for in vitro binding and in situ hybridization experiments. RESULTS: Acutely, 0.3 and 1mg/kg of WIN55,212-2 produced hypolocomotion, which was sustained for the next 2 measurements, compared to vehicle. Repeated administration of WIN55,212-2 decreased the mRNA levels of the D2 autoreceptors in substantia nigra and ventral tegmental area and increased D1 receptor mRNA and binding in nucleus accumbens. Furthermore, both dopamine receptor and transporter binding and mRNA levels were decreased in substantia nigra. Moreover, repeated administration of WIN55,212-2 decreased GABAA receptor binding levels in dorsal striatum and substantia nigra. CONCLUSIONS: Our data indicate that chronic WIN55,212-2 administration results in sustained effects on locomotor activity, similar to those observed after acute administration, and modulates the dopaminergic and GABAergic systems in a region-, dose-, and neurotransmitter-selective manner.