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1.
J Biol Regul Homeost Agents ; 24(3): 297-306, 2010.
Article in English | MEDLINE | ID: mdl-20846477

ABSTRACT

Amyloid-beta (Abeta) peptide aggregation forms such as soluble oligomers (O) have a causal role in neuronal dysfunction and death associated with Alzheimer?s Disease (AD). The main efforts for the development of neuroprotective drugs are therefore focused on preventing Abeta production, aggregation or downstream neurotoxic events. We therefore investigated the effect of guanosine (GUO), a guanine based purine, that exerts neurotrophic and neuroprotective effects. The GUO showed the ability to reduce neuronal death in terms of apoptosis, but not necrosis, elicited by Abeta1-42O in human neuroblastoma SH-SY5Y cells. The neuroprotective effect was recorded only when the GUO was added simultaneously to treatment of the SH-SY5Y cells with Abeta1-42O. By contrast, the GUO treatment of SH-SY5Y cells before and after the appearance of beta1-42O toxicity had no neuroprotective effects. The employment of specific inhibitors showed the involvement of neuronal survival pathways, such as PI3K?Akt and MAPK-ERK for the GUO anti-apoptotic effects observed. In parallel, the SH-SY5Y cells treated with GUO, in experimental conditions similar to those adopted to evaluate neuronal death, showed a marked decrease of the early reactive oxygen species formation induced by Abeta1-42O and pro-oxidant H2O2. In the same neuronal model, GUO was also shown to inhibit the extra- and intra-cellular Abeta1-42 release as well as the beta-secretase activity evoked by H2O2 pro-oxidant action. Based on these findings, GUO and other guanine based purines appear to be a promising class of compounds with neuroprotective properties that may play an important role in the therapy of AD.


Subject(s)
Amyloid beta-Peptides/toxicity , Guanosine/pharmacology , Neuroblastoma/metabolism , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Peptide Fragments/toxicity , Antioxidants/pharmacology , Cell Line, Tumor , Humans , MAP Kinase Signaling System , Neuroblastoma/pathology , Proto-Oncogene Proteins c-akt/metabolism
2.
J Food Sci ; 75(1): C94-9, 2010.
Article in English | MEDLINE | ID: mdl-20492158

ABSTRACT

Strawberries (Fragaria ananassa L., cv. favette) were studied to investigate the influence of cultivation practices (biodynamic, conventional) on the synthesis of bioactive molecules (ascorbic acid, ellagic acid, anthocyanins, flavonols) and to evaluate their antioxidant activity. Additionally, the in vitro bioactivity, in terms of antioxidant and antiproliferative activity, of the same strawberry samples in human colon carcinoma (Caco-2) cells was also studied. Compared to conventional strawberries, biodynamic fruits had a significantly higher content of ascorbic acid (P < 0.01), pelargonidin-3-glucoside (P < 0.05), cyanidin-3-glucoside (P < 0.01), ellagic acid (P < 0.01), quercetin, and kaempferol (both P < 0.01). Antioxidant activity of biodynamic strawberry crude extract was significantly higher than that of the conventional one (P < 0.05); in addition, while the antioxidant activity of water-soluble fraction was very similar in both biodynamic and conventional strawberries, that of water-insoluble fraction of biodynamic fruits was significantly higher (P < 0.05). The same crude extract of biodynamic strawberry samples effectively corresponded to an increase of bioactivity, in terms of both cellular antioxidant activity and antiproliferative activity, in Caco-2 cells differentiated to normal intestinal epithelia and in undifferentiated Caco-2, respectively. Further studies are needed to confirm whether the practice of biodynamic agriculture is likely to increase the bioactivity of other varieties of fruits and vegetables.


Subject(s)
Antioxidants/metabolism , Fragaria/growth & development , Anthocyanins/biosynthesis , Anthocyanins/pharmacology , Antioxidants/pharmacology , Ascorbic Acid/biosynthesis , Caco-2 Cells/cytology , Caco-2 Cells/drug effects , Caco-2 Cells/metabolism , Cell Division/drug effects , Cell Membrane/drug effects , Cell Membrane/metabolism , Cytosol/drug effects , Cytosol/metabolism , Ellagic Acid/metabolism , Ellagic Acid/pharmacology , Flavonols/biosynthesis , Fragaria/metabolism , Humans , Quercetin/metabolism , Quercetin/pharmacology
3.
Eur J Nutr ; 45(3): 152-8, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16096701

ABSTRACT

BACKGROUND: Consumers consider plant food products from organic origin healthier than the corresponding conventional plant foods. Clear experimental evidence supporting this assumption is still lacking. AIM OF THE STUDY: To determine if the organic red oranges have a higher phyto-chemical content (i. e., phenolics, anthocyanins and ascorbic acid), total antioxidant activity and in vitro bioactivity, in terms of protective effect against oxidative damage at cellular level, than nonorganic red oranges. METHODS: Total phenolics were measured using the Folin Ciocalteau assay, while total anthocyanins and ascorbic acid levels were determined by spectrophotometric and HPLC analysis, respectively. In addition, the total antioxidant activity of red orange extracts was measured by the ABTS(*+) test. The ability of red orange extracts to counteract conjugated diene containing lipids and free radical production in cultured rat cardiomyocytes and differentiated Caco-2 cells, respectively, was assessed. RESULTS: Organic oranges had significantly higher total phenolics, total anthocyanins and ascorbic acid levels than the corresponding non-organic oranges (all p < 0.05). Moreover, the organic orange extracts had a higher total antioxidant activity than non-organic orange extracts (p < 0.05). In addition, our results indicate that red oranges have a strong capacity of inhibiting the production of conjugated diene containing lipids and free radicals in rat cardiomyocytes and differentiated Caco-2 cells, respectively. Statistically higher levels of antioxidant activity in both cell models were found in organically grown oranges as compared to those produced by integrated agriculture practice. CONCLUSIONS: Our results clearly show that organic red oranges have a higher phytochemical content (i. e., phenolics, anthocyanins and ascorbic acid), total antioxidant activity and bioactivity than integrated red oranges. Further studies are needed to confirm whether the organic agriculture practice is likely to increase the antioxidant activity of other varieties of fruits and vegetables.


Subject(s)
Agriculture/methods , Antioxidants/analysis , Citrus sinensis/chemistry , Food, Organic , Anthocyanins/analysis , Anthocyanins/metabolism , Antioxidants/metabolism , Ascorbic Acid/analysis , Ascorbic Acid/metabolism , Caco-2 Cells/metabolism , Chromatography, High Pressure Liquid/methods , Food, Organic/analysis , Humans , Hydroxybenzoates/analysis , Hydroxybenzoates/metabolism , Myocytes, Cardiac/metabolism , Oxidation-Reduction
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