Resveratrol Abstracts 1

© 2012

Resveratrol Protects Rats from Abeta-induced Neurotoxicity by the Reduction of iNOS Expression and Lipid Peroxidation

            (Huang, Lu et al. 2011) Download

Alzheimer disease (AD) is an age-dependent neurodegenerative disease characterized by the formation of beta-amyloid (Abeta)-containing senile plaque. The disease could be induced by the administration of Abeta peptide, which was also known to upregulate inducible nitric oxide synthase (iNOS) and stimulate neuronal apoptosis. The present study is aimed to elucidate the cellular effect of resveratrol, a natural phytoestrogen with neuroprotective activities, on Abeta-induced hippocampal neuron loss and memory impairment. On adult Sprague-Dawley rats, we found the injection of Abeta could result in a significant impairment in spatial memory, a marked increase in the cellular level of iNOS and lipid peroxidation, and an apparent decrease in the expression of heme oxygenase-1 (HO-1). By combining the treatment with Abeta, resveratrol was able to confer a significant improvement in spatial memory, and protect animals from Abeta-induced neurotoxicity. These neurological protection effects of resveratrol were associated with a reduction in the cellular levels of iNOS and lipid peroxidation and an increase in the production of HO-1. Moreover, the similar neurological and cellular response were also observed when Abeta treatment was combined with the administration of a NOS inhibitor, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME). These findings strongly implicate that iNOS is involved in the Abeta-induced lipid peroxidation and HO-1 downregulation, and resveratrol protects animals from Abeta-induced neurotoxicity by suppressing iNOS production.

Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease

            (Karuppagounder, Pinto et al. 2009) Download

Resveratrol, a polyphenol found in red wine, peanuts, soy beans, and pomegranates, possesses a wide range of biological effects. Since resveratrol's properties seem ideal for treating neurodegenerative diseases, its ability to diminish amyloid plaques was tested. Mice were fed clinically feasible dosages of resveratrol for forty-five days. Neither resveratrol nor its conjugated metabolites were detectable in brain. Nevertheless, resveratrol diminished plaque formation in a region specific manner. The largest reductions in the percent area occupied by plaques were observed in medial cortex (-48%), striatum (-89%) and hypothalamus (-90%). The changes occurred without detectable activation of SIRT-1 or alterations in APP processing. However, brain glutathione declined 21% and brain cysteine increased 54%. The increased cysteine and decreased glutathione may be linked to the diminished plaque formation. This study supports the concept that onset of neurodegenerative disease may be delayed or mitigated with use of dietary chemo-preventive agents that protect against beta-amyloid plaque formation and oxidative stress.

Melatonin Potentiates the Neuroprotective Properties of Resveratrol Against Beta-Amyloid-Induced Neurodegeneration by Modulating AMP-Activated Protein Kinase Pathways

            (Kwon, Kim et al. 2010) Download

BACKGROUND AND PURPOSE: Recent studies have demonstrated that resveratrol (RSV) reduces the incidence of age-related macular degeneration, Alzheimer's disease (AD), and stroke, while melatonin (MEL) supplementation reduces the progression of the cognitive impairment in AD patients. The purpose of this investigation was to assess whether the co-administration of MEL and RSV exerts synergistic effects on their neuroprotective properties against beta-amyloid (Abeta)-induced neuronal death. METHODS: The neuroprotective effects of co-treatment with MEL and RSV on Abeta1-42-induced cell death, was measured by MTT reduction assay. Abeta1-42 caused an increase in intracellular levels of reactive oxygen species (ROS), as assessed by H(2)-DCF-DA dye, and a reduction of total glutathione (GSH) levels and mitochondrial membrane potential, as assessed using monochlorobimane and rhodamine 123 fluorescence, respectively. Western blotting was used to investigate the intracellular signaling mechanism involved in these synergic effects. RESULTS: We treated a murine HT22 hippocampal cell line with MEL or RSV alone or with both simultaneously. MEL and RSV alone significantly attenuated ROS production, mitochondrial membrane-potential disruption and the neurotoxicity induced by Abeta1-42. They also restored the Abeta1-42-induced depletion of GSH, back to within its normal range and prevented the Abeta1-42-induced activation of glycogen synthase kinase 3beta (GSK3beta). However, co-treatment with MEL and RSV did not exert any significant synergistic effects on either the recovery of the Abeta1-42-induced depletion of GSH or on the inhibition of Abeta1-42-induced GSK3beta activation. Abeta1-42 treatment increased AMP-activated protein kinase (AMPK) activity, which is associated with subsequent neuronal death. We demonstrated that MEL and RSV treatment inhibited the phosphorylation of AMPK. CONCLUSIONS: Together, our results suggest that co-administration of MEL and RSV acts as an effective treatment for AD by attenuating Abeta1-42-induced oxidative stress and the AMPK-dependent pathway.


Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides

            (Marambaud, Zhao et al. 2005) Download

Several epidemiological studies indicate that moderate consumption of wine is associated with a lower incidence of Alzheimer's disease. Wine is enriched in antioxidant compounds with potential neuroprotective activities. However, the exact molecular mechanisms involved in the beneficial effects of wine intake on the neurodegenerative process in Alzheimer's disease brain remain to be clearly defined. Here we show that resveratrol (trans-3,4',5-trihydroxystilbene), a naturally occurring polyphenol mainly found in grapes and red wine, markedly lowers the levels of secreted and intracellular amyloid-beta (Abeta) peptides produced from different cell lines. Resveratrol does not inhibit Abeta production, because it has no effect on the Abeta-producing enzymes beta- and gamma-secretases, but promotes instead intracellular degradation of Abeta via a mechanism that involves the proteasome. Indeed, the resveratrol-induced decrease of Abeta could be prevented by several selective proteasome inhibitors and by siRNA-directed silencing of the proteasome subunit beta5. These findings demonstrate a proteasome-dependent anti-amyloidogenic activity of resveratrol and suggest that this natural compound has a therapeutic potential in Alzheimer's disease.

Neuroprotective properties of resveratrol and derivatives

            (Richard, Pawlus et al. 2011) Download

Stilbenoid compounds consist of a family of resveratrol derivatives. They have demonstrated promising activities in vitro and in vivo that indicate they may be useful in the prevention of a wide range of pathologies, such as cardiovascular diseases and cancers, as well have anti-aging effects. More recently stilbenoid compounds have shown promise in the treatment and prevention of neurodegenerative disorders, such as Huntington's, Parkinson's, and Alzheimer's diseases. This paper primarily focuses on the impact of stilbenoids in Alzheimer's disease and more specifically on the inhibition of beta-amyloid peptide aggregation.

Resveratrol as a therapeutic agent for neurodegenerative diseases

            (Sun, Wang et al. 2010) Download

Excess production of reactive oxygen species in the brain has been implicated as a common underlying risk factor for the pathogenesis of a number of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In recent years, there is considerable interest concerning investigation of antioxidative and anti-inflammatory effects of phenolic compounds from different botanical sources. In this review, we first describe oxidative mechanisms associated with stroke, AD, and PD, and subsequently, we place emphasis on recent studies implicating neuroprotective effects of resveratrol, a polyphenolic compound derived from grapes and red wine. These studies show that the beneficial effects of resveratrol are not only limited to its antioxidant and anti-inflammatory action but also include activation of sirtuin 1 (SIRT1) and vitagenes, which can prevent the deleterious effects triggered by oxidative stress. In fact, SIRT1 activation by resveratrol is gaining importance in the development of innovative treatment strategies for stroke and other neurodegenerative disorders. The goal here is to provide a better understanding of the mode of action of resveratrol and its possible use as a potential therapeutic agent to ameliorate stroke damage as well as other age-related neurodegenerative disorders.

Therapeutic potential of resveratrol in Alzheimer's disease

            (Vingtdeux, Dreses-Werringloer et al. 2008) Download

Several epidemiological studies indicate that moderate consumption of red wine is associated with a lower incidence of dementia and Alzheimer's disease. Red wine is enriched in antioxidant polyphenols with potential neuroprotective activities. Despite scepticism concerning the bioavailability of these polyphenols, in vivo data have clearly demonstrated the neuroprotective properties of the naturally occurring polyphenol resveratrol in rodent models for stress and diseases. Furthermore, recent work in cell cultures and animal models has shed light on the molecular mechanisms potentially involved in the beneficial effects of resveratrol intake against the neurodegenerative process in Alzheimer's disease.

Cellular and molecular effects of resveratrol in health and disease

            (Yu, Fu et al. 2012) Download

Resveratrol, a natural polyphenol abundantly found in grape skins and red wine, possesses diverse biochemical and physiological actions, including anti-inflammatory, anti-oxidation, anti-proliferation and promotion of differentiation, and chemopreventive effects. Recently, it is attracting increased attention due to its health benefits, especially in common age-related diseases such as cardiovascular disease, cancer, type 2 diabetes, and neurological conditions. In this review, we discuss the latest cellular and molecular findings that account for the beneficial actions of resveratrol. J. Cell. Biochem. 113: 752-759, 2012. (c) 2011 Wiley Periodicals, Inc.


References

Huang, T. C., K. T. Lu, et al. (2011). "Resveratrol Protects Rats from Abeta-induced Neurotoxicity by the Reduction of iNOS Expression and Lipid Peroxidation." PLoS One 6(12): e29102.

Karuppagounder, S. S., J. T. Pinto, et al. (2009). "Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease." Neurochem Int 54(2): 111-8.

Kwon, K. J., H. J. Kim, et al. (2010). "Melatonin Potentiates the Neuroprotective Properties of Resveratrol Against Beta-Amyloid-Induced Neurodegeneration by Modulating AMP-Activated Protein Kinase Pathways." J Clin Neurol 6(3): 127-37.

Marambaud, P., H. Zhao, et al. (2005). "Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides." J Biol Chem 280(45): 37377-82.

Richard, T., A. D. Pawlus, et al. (2011). "Neuroprotective properties of resveratrol and derivatives." Ann N Y Acad Sci 1215: 103-8.

Sun, A. Y., Q. Wang, et al. (2010). "Resveratrol as a therapeutic agent for neurodegenerative diseases." Mol Neurobiol 41(2-3): 375-83.

Vingtdeux, V., U. Dreses-Werringloer, et al. (2008). "Therapeutic potential of resveratrol in Alzheimer's disease." BMC Neurosci 9 Suppl 2: S6.

Yu, W., Y. C. Fu, et al. (2012). "Cellular and molecular effects of resveratrol in health and disease." J Cell Biochem 113(3): 752-9.