27 March 2020 In Dementia

With an increase in life expectancy, the incidence of chronic degenerative pathologies such as dementia has progressively risen. Cognitive impairment leads to the gradual loss of skills, which results in substantial personal and financial cost at the individual and societal levels. Grapes and wines are rich in healthy compounds, which may help to maintain homeostasis and reduce the risk of several chronic illnesses, including dementia. This review analyzed papers that were systematically searched in PubMed, MEDLINE, Embase, and CAB-Abstract, using the association between grapes (or their derivatives) and their effects on cognitive functions in humans. Analysis was restricted to epidemiological and randomized-controlled studies. Consumption of grape juice (200-500 mL/day) and/or light-to-moderate wine (one to four glasses/day) was generally associated with improved cognitive performance, while the results for other alcoholic beverages were controversial and inconclusive. Bioactive molecules contained in grapes and wine were also considered, with particular attention paid to resveratrol. Due to the relatively high doses required (150-1000 mg/day) for bioactivity coupled with its low bioavailability, resveratrol is only one of the possible grape-derived compounds that may partly underpin the beneficial effects of grapes on the central nervous system.

24 October 2019 In Cardiovascular System

Wine is a popular alcoholic beverage that has been consumed for hundreds of years. Benefits from moderate alcohol consumption have been widely supported by the scientific literature and, in this line, red wine intake has been related to a lesser risk for coronary heart disease (CHD).

Experimental studies and meta-analyses have mainly attributed this outcome to the presence in red wine of a great variety of polyphenolic compounds such as resveratrol, catechin, epicatechin, quercetin, and anthocyanin. Resveratrol is considered the most effective wine compound with respect to the prevention of CHD because of its antioxidant properties.

The mechanisms responsible for its putative cardioprotective effects would include changes in lipid profiles, reduction of insulin resistance, and decrease in oxidative stress  of low-density lipoprotein cholesterol (LDL-C).

The aim of this review is to summarize the accumulated evidence correlating moderate red wine consumption with prevention of CHD by focusing on the different mechanisms underlying this relationship. Furthermore, the chemistry of wine as well as chemical factors that influence the composition of the bioactive components of red wine are also discussed.

09 August 2019 In Phenolic compounds

Resveratrol is a natural non-flavonoid polyphenol found in red wine, which has numerous pharmacological properties including anti-stress and antidepressant-like abilities. However, whether the antidepressant- and anxiolytic-like effects of resveratrol are related to the inhibition of phosphodiesterase 4 (PDE4) and its subtypes remains unknown. The same holds true for the subsequent cAMP-dependent pathway. The first set of studies investigated whether resveratrol exhibited neuroprotective effects against corticosterone-induced cell lesion as well as its underlying mechanism. We found that 100muM corticosterone induced PDE2A, PDE3B, PDE4A, PDE4D, PDE10 and PDE11 expression in HT-22cells, which results in significant cell lesion. However, treatment with resveratrol increased cell viability in a dose- and time-dependent manner. These effects seem related to the inhibition of PDE4D, as evidenced by resveratrol dose-dependently decreasing PDE4D expression. In addition, the PKA inhibitor H89 reversed resveratrol's effects on cell viability. Resveratrol prevented corticosterone-induced reduction in cAMP, pVASP(s157), pCREB, and BDNF levels, indicating that cAMP signaling is involved in resveratrol-induced neuroprotective effects. Not to mention, PDE4D knockdown by PDE4D siRNA potentiated the effect of low dose of resveratrol on cAMP, pVASP, pCREB, and BDNF expression, while PDE4D overexpression reversed the effect of high dose of resveratrol on the expression of the above proteins. Finally, the subsequent in vivo data supports the in vitro findings, suggesting that resveratrol-induced antidepressant- and anxiolytic-like effects are mediated by PDE4D. Overall, these findings support the hypothesis that PDE4D-mediated cAMP signaling plays an important role in resveratrol's protective effects on stress-induced depression- and anxiety-like behavior.

03 June 2019 In Phenolic compounds

BACKGROUND: The health-promoting and disease-limiting abilities of resveratrol, a natural polyphenol, has led to considerable interest in understanding the mechanisms of its therapeutic actions. The polyphenolic rings of resveratrol enable it to react with and detoxify otherwise injurious oxidants. Whilst the protective actions of resveratrol are commonly ascribed to its antioxidant activity, here we show that this is a misconception.

METHODS: The ability of resveratrol to oxidise cyclic guanosine-3',5'-monophosphate (cGMP)-dependent protein kinase 1alpha (PKG1alpha) was assessed in isolated rat aortic smooth muscle cells, and the mechanism of action of this polyphenol characterised using in vitro experiments, mass spectrometry and electron paramagnetic resonance. The blood pressure of wild-type and C42S knock-in mice was assessed using implanted telemetry probes. Mice were made hypertensive by administration of angiotensin II via osmotic mini-pumps and blood pressure monitored during 15 days of feeding with chow diet containing vehicle or resveratrol.

RESULTS: Oxidation of the phenolic rings of resveratrol paradoxically leads to oxidative modification of proteins, explained by formation of a reactive quinone that oxidises the thiolate side chain of cysteine residues - events that were enhanced in cells under oxidative stress. Consistent with these observations and its ability to induce vasodilation, resveratrol induced oxidative activation of PKG1alpha and lowered blood pressure in hypertensive wild-type mice, but not C42S PKG1alpha knock-in mice that are resistant to disulfide activation.

CONCLUSIONS: Resveratrol mediates lowering of blood pressure by paradoxically inducing protein oxidation, especially during times of oxidative stress, a mechanism that may be a common feature of 'antioxidant' molecules.

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