Effect of resveratrol and catechin on PC12 tyrosine kinase activities and their synergistic protection from beta-amyloid toxicity.
ABSTRACT beta-Amyloid peptide (beta-AP) is the main component of amyloid deposits around the cerebral vessel and in the brain parenchyma in Alzheimer's disease and Down's syndrome. In vitro studies in neuronal cells or in PC12 and Hela cell lines have shown that the aggregate form of beta-AP is toxic. Many genetic and environmental factors including metal ions, proteoglycans, plasma proteins and antioxidants modify beta-AP toxicity. We investigated the effect of two plant polyphenols--resveratrol and catechin--on soluble and particulate tyrosine kinase activity from PC12 cells and the protective action of these compounds against beta-AP (1-41) toxicity. beta-AP (1-41) decreased PC12 viability with an IC50 value of 1.1 +/- 0.14 x 10(-8) M. Resveratrol and catechin protected PC12 cells from beta-AP (1-41) toxicity. With 25 microM resveratrol the IC50 value increased to 2.2 +/- 0.19 x 10(-7) M. In the presence of beta-AP (1-41) resveratrol showed a concentration-dependent biphasic effect, and at a concentration of up to 40 microM it protected PC12 cells from beta-AP (1-41) toxicity. At concentrations higher than 40 microM, an inhibitory activity on cell proliferation appeared. This antiproliferative effect was also seen in the absence of beta-AP (1-41). With 100 microM catechin the IC50 value increased from 1.1 +/- 0.14 x 10(-8) M to 3.2 +/- 0.25 x 10(-7) M beta-AP (1-41). The protective effect was concentration dependent. Resveratrol and catechin had a synergistic protective action. In the presence of 40 microM catechin and 10 microM resveratrol or 20 microM resveratrol and 10 microM catechin, the toxicity determined by 10(-7) M beta-AP (1-41) was almost completely removed. Resveratrol and catechin had different effects on PC12 tyrosine kinase activity. With peptide 1-17 of gastrin as substrate, resveratrol inhibited particulate tyrosine kinases while it had no effect on soluble activity. With the same substrate, catechin increased the activity of soluble fraction while it inhibited particulate activity. When peptide 6-20 of cell division kinase p34cdc2 was utilized, catechin showed an opposite effect, inhibiting soluble tyrosine kinase activity and increasing particulate activity. With peptide 6-20, resveratrol inhibited both soluble and particulate activities. These results demonstrate that resveratrol and catechin have different activities on the signal transduction pathway involving protein phosphorylation. These differences may contribute not only to the different effects of these compounds on PC12 growth but also to the synergistic effect against beta-AP (1-41) toxicity. The different activity of resveratrol and catechin on signal transduction pathways, as well as the differences in metal chelation, partition coefficient between water and lipids, hydrogen donation redox potential and enzyme inhibition may be at least in part based on synergistic protection against beta-AP (1-41) toxicity.
Article: Maternal dietary supplementation with pomegranate juice is neuroprotective in an animal model of neonatal hypoxic-ischemic brain injury.[show abstract] [hide abstract]
ABSTRACT: Neonatal hypoxic-ischemic brain injury remains a significant cause of morbidity and mortality and lacks effective therapies for prevention and treatment. Recently, interest in the biology of polyphenol compounds has led to the discovery that dietary supplementation with foods rich in polyphenols (e.g. blueberries, green tea extract) provides neuroprotection in adult animal models of ischemia and Alzheimer's disease. We sought to determine whether protection of the neonatal brain against a hypoxic-ischemic insult could be attained through supplementation of the maternal diet with pomegranate juice, notable for its high polyphenol content. Mouse dams were provided ad libitum access to drinking water with pomegranate juice, at one of three doses, as well as plain water, sugar water, and vitamin C water controls during the last third of pregnancy and throughout the duration of litter suckling. At postnatal day 7, pups underwent unilateral carotid ligation followed by exposure to 8% oxygen for 45 min. Brain injury was assessed histologically after 1 wk (percentage of tissue area loss) and biochemically after 24 h (caspase-3 activity). Dietary supplementation with pomegranate juice resulted in markedly decreased brain tissue loss (>60%) in all three brain regions assessed, with the highest pomegranate juice dose having greatest significance (p < or = 0.0001). Pomegranate juice also diminished caspase-3 activation by 84% in the hippocampus and 64% in the cortex. Ellagic acid, a polyphenolic component in pomegranate juice, was detected in plasma from treated but not control pups. These results demonstrate that maternal dietary supplementation with pomegranate juice is neuroprotective for the neonatal brain.Pediatric Research 06/2005; 57(6):858-64. · 2.70 Impact Factor
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ABSTRACT: The impact of water deficit on stilbene biosynthesis in wine grape (Vitis vinifera) berries was investigated. Water deficit increased the accumulation of trans-piceid (the glycosylated form of resveratrol) by 5-fold in Cabernet Sauvignon berries but not in Chardonnay. Similarly, water deficit significantly increased the transcript abundance of genes involved in the biosynthesis of stilbene precursors in Cabernet Sauvignon. Increased expression of stilbene synthase, but not that of resveratrol-O-glycosyltransferase, resulted in increased trans-piceid concentrations. In contrast, the transcript abundance of the same genes declined in Chardonnay in response to water deficit. Twelve single nucleotide polymorphisms (SNPs) were identified in the promoters of stilbene synthase genes of Cabernet Sauvignon, Chardonnay, and Pinot Noir. These polymorphisms resulted in eight changes within the predicted cis regulatory elements in Cabernet Sauvignon and Chardonnay. These results suggest that cultivar-specific molecular mechanisms might exist that control resveratrol biosynthesis in grapes.Journal of Agricultural and Food Chemistry 01/2011; 59(1):289-97. · 2.82 Impact Factor