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Roles of resveratrol and other grape-derived polyphenols in Alzheimer's disease prevention and treatment.

ABSTRACT: Alzheimer's disease (AD) is a devastating disorder that strikes 1 in 10 Americans over the age of 65, and almost half of all Americans over 85 years old. The odds of an individual developing AD double every five years after the age of 65. While it has become increasingly common to meet heart attack or cancer survivors, there are no AD survivors. There is mounting evidence that dietary polyphenols, including resveratrol, may beneficially influence AD. Based on this consideration, several studies reported in the last few years were designed to validate sensitive and reliable translational tools to mechanistically characterize brain bioavailable polyphenols as disease-modifying agents to help prevent the onset of AD dementia and other neurodegenerative disorders. Several research groups worldwide with expertise in AD, plant biology, nutritional sciences, and botanical sciences have reported very high quality studies that ultimately provided the necessary information showing that polyphenols and their metabolites, which come from several dietary sources, including grapes, cocoa etc., are capable of preventing AD. The ultimate goal of these studies was to provide novel strategies to prevent the disease even before the onset of clinical symptoms. The studies discussed in this review article provide support that the information gathered in the last few years of research will have a major impact on AD prevention by providing vital knowledge on the protective roles of polyphenols, including resveratrol. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.

SUBMITTER: Pasinetti GM

PROVIDER: S-EPMC4380832 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Roles of resveratrol and other grape-derived polyphenols in Alzheimer's disease prevention and treatment.

Pasinetti Giulio Maria GM Wang Jun J Ho Lap L Zhao Wei W Dubner Lauren L

Biochimica et biophysica acta 20141012 6

Alzheimer's disease (AD) is a devastating disorder that strikes 1 in 10 Americans over the age of 65, and almost half of all Americans over 85 years old. The odds of an individual developing AD double every five years after the age of 65. While it has become increasingly common to meet heart attack or cancer survivors, there are no AD survivors. There is mounting evidence that dietary polyphenols, including resveratrol, may beneficially influence AD. Based on this consideration, several studies ...[more]

PMID: 25315300

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Project description:Resveratrol (RES) is a natural polyphenolic non-flavonoid compound present in grapes, mulberries, peanuts, rhubarb and in several other plants. Numerous health effects have been related with its intake, such as anti-carcinogenic, anti-inflammatory and brain protective effects. The neuroprotective effects of RES in neurological diseases, such as Alzheimer's (AD) and Parkinson's (PD) diseases, are related to the protection of neurons against oxidative damage and toxicity, and to the prevention of apoptotic neuronal death. In brain cancer, RES induces cell apoptotic death and inhibits angiogenesis and tumor invasion. Despite its great potential as therapeutic agent for the treatment of several diseases, RES exhibits some limitations. It has poor water solubility and it is chemically instable, being degraded by isomerization once exposed to high temperatures, pH changes, UV light, or certain types of enzymes. Thus, RES has low bioavailability, limiting its biological and pharmacological benefits. To overcome these limitations, RES can be delivered by nanocarriers. This field of nanomedicine studies how the drug administration, pharmacokinetics, and pharmacodynamics are affected by the use of nanosized materials. The role of nanotechnology, in the prevention and treatment of neurological diseases, arises from the necessity to mask the physicochemical properties of therapeutic drugs to prolong the half-life and to be able to cross the blood-brain barrier (BBB). This can be achieved by encapsulating the drug in a nanoparticle (NP), which can be made of different kinds of materials. An increasing trend to encapsulate and direct RES to the brain has been observed. RES has been encapsulated in many different types of nanosystems, as liposomes, lipid and polymeric NPs. Furthermore, some of these nanocarriers have been modified with targeting molecules able to recognize the brain areas. Then, this article aims to overview the RES benefits and limitations in the treatment of neurological diseases, as the different nanotechnology strategies to overcome these limitations.

Project description:BackgroundTo evaluate the efficacy and pharmacological mechanisms of resveratrol in Alzheimer's disease (AD) patients.MethodsWe conducted a thorough exploration of existing randomized controlled trials concerning the treatment of Alzheimer's disease patients using resveratrol, utilizing accessible open databases. Quantitative variables were represented as a standardized mean difference (SMD), accompanied by a 95% confidence interval (CI). Additionally, we examined the potential targets and plausible pathways associated with the impact of resveratrol on Alzheimer's disease using network pharmacology techniques.ResultsOur meta-analysis comprised five trials involving 271 AD patients, of whom 139 received resveratrol treatment and 132 received placebo treatment. Compared with placebo therapy, resveratrol treatment resulted in a significant improvement in Alzheimer's Disease Cooperative Study- Activities of Daily Living (ADAS-ADL) scores (SMD=0.51; 95% CI, 0.24 to 0.78) and cerebrospinal fluid (CSF) Aβ40 (SMD=0.84; 95% CI, 0.21 to 1.47) and plasma Aβ40 levels (SMD=0.43; 95% CI, 0.07 to 0.79). However, the improvement in the resveratrol-treated group compared with the placebo treatment group on the Mini-Mental State Examination (MMSE) score, CSF Aβ42 and plasma Aβ42 levels, and brain volume was not significant. There were no noteworthy statistical variances in the occurrence of adverse effects noted between the two groups. The outcomes of network pharmacology divulged that the principal enriched interaction pathway between resveratrol and Alzheimer's disease is primarily concentrated within the PI3K signaling pathways. Resveratrol's potential key targets for the treatment of AD include MAKP1, HRAS, EGFR, and MAPK2K1.ConclusionWhile having a high safety profile, resveratrol has efficacy in AD patients to a certain extent, and more data are required to validate the efficacy of resveratrol for the treatment of AD in the future. Suppression of the PI3K signaling pathways could hold significant importance in the treatment of AD patients using resveratrol.

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Roles of resveratrol and other grape-derived polyphenols in Alzheimer's disease prevention and treatment.

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Roles of resveratrol and other grape-derived polyphenols in Alzheimer's disease prevention and treatment.

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