Frataxin mRNA isoforms in FRDA patients and normal subjects: effect of tocotrienol supplementation.

Friedreich's ataxia (FRDA) is caused by deficient expression of the mitochondrial protein frataxin involved in the formation of iron-sulphur complexes, and by consequent oxidative stress. We analysed low-dose tocotrienol supplementation effects on the expression of the three splice variant isoforms (FXN-1, FXN-2 and FXN-3) in mononuclear blood cells of FRDA patients and healthy subjects. In FRDA patients, tocotrienol leads to a specific and significant increase of FXN-3 expression, while not affecting FXN-1 and FXN-2 expression. Since no structural and functional details were available for FNX-2 and FXN-3, 3D-models were built. FXN-1, the canonical isoform, was then docked on the human iron-sulphur complex and functional interactions were computed; when FXN-1 was replaced by FXN-2 or FNX-3, we found that the interactions were maintained, thus suggesting a possible biological role for both isoforms in human cells. Finally, in order to evaluate whether tocotrienol enhancement of FXN-3 was mediated by an increase in peroxisome proliferator-activated receptor-\uf067 (PPARG), PPARG expression was evaluated. At low dose of tocotrienol, the increase of FXN-3 expression appeared to be independent of PPARG expression. Our data show that it is possible to modulate the mRNA expression of the minor frataxin isoforms, and that they may have a functional role

Oxidative stress and erythrocyte membrane alterations in children with autism: correlation with clinical features

It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na+/K+-ATPase activity (-66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-\u3c93 with a consequent increase in \u3c96/\u3c93 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD

Extracts of cocoa and chocolate a comparative valuation of functional efficacy

Chocolate antioxidant properties are often claimed, however they are frequently different from the parent natural sources due to the industry or artisan transformation. In this study we report the preliminary results of antioxidant capacity and total phenolic content of cocoa nibs, cocoa masses and corresponding chocolate bars with different percentages of cocoa from differen origin. The antioxidant capacity of the different samples was measured by two different assays (DPPH and FRAP tests). Folin–Ciocalteu reagent was used to assess the total phenolics content. The masses showed a higher antioxidant power than the nibs, and this has been attributed to the fact that in the nibs is still present the lipid part which will form the cocoa butter. Ours results showed that the extra dark cocoa bar 100% cocoa chocolate is the best in terms of total polyphenols content and in terms of antioxidant capacity according to the DPPH and FRAP tests. Also the bars of Organic dark chocolate 80%, dark Tanzania 80% and Trinidad 80% products are good in all respects

Novel molecular combination deriving from natural aminoacids and polyphenols: Design, synthesis and free-radical scavenging activities

Following the recent output of scientific publications in the matter of synergic activity between different antioxidants, we have undertaken the present study with the aim to synthesize new molecules with radical-scavengers activity based on the conjugation of bioactive portions (i.e. phenols, cysteine, methionine or tyrosine), characterized by different structures and mechanisms of action, to promote the simultaneous quenching of different radical species in the site of the oxidative damage. In this context, derivatives of phenolic acid, aminoacids and dopamine have been also prepared. The newly synthesized compounds were evaluated in vitro applying specific and complementary antioxidant test such as DPPH assay and ORAC test As emerged from the evaluation, prerequisites for the activity of the synthesized molecules were: i) the maintenance of at least two hydroxylic groups on the aromatic moiety of phenolic portion, ii) the presence of a spacer between the aromatic moiety and the carbonilic grou

Synthesis, Antioxidant and Antimicrobial Activity of a New Phloridzin Derivative for Dermo-Cosmetic Applications

The phenolic compound phloridzin (phloretin 2′-O-glucoside, variously named phlorizin, phlorrhizin, phlorhizin or phlorizoside) is a prominent member of the chemical class of dihydrochalcones, which are phenylpropanoids. Phloridzin is specifically found in apple and apple juice and known for its biological properties. In particular we were attracted by potential dermo-cosmetic applications. Here we report the synthesis, stability studies and antimicrobial activity of compound F2, a new semi-synthetic derivative of phloridzin. The new derivative was also included in finished formulations to evaluate its stability with a view to a potential topical use. Stability studies were performed by HPLC; PCL assay and ORAC tests were used to determine the antioxidant activity. F2 presented an antioxidant activity very close to that of the parent phloridzin, but, unlike the latter, was more stable in formulations. To further explore potential health claims, antifungal activity of phloridzin and its derivative F2 were determined; the results, however, were rather low; the highest value was 31,6% of inhibition reached by F2 on Microsporum canis at the highest dose

VPP: VERBASCOSIDE PENTA PROPIONATE, A NOVEL MULTIFUNCTIONAL INGREDIENT, DERIVING FROM TRADITIONAL REMEDIES INSPIRATION

The biological properties of verbascoside (V) comprise antioxidant, anti-inflammatory, photoprotective and chelating. The Plantago lanceolata is a perennial herbaceous plant spread throughout most of Europe and V is one of the most interesting components of the extracts and decoctions, that have a long history of use in traditional medicine. Starting from this finding we developed Buddleja davidii cell cultures, expressing very high concentrations of V to be used as a convenient source of the same. Moreover, in order to overcome low stability in biological medium we developed a prodrug (VPP), in order to make it more lipid-soluble. The parent as well as the synthesized compounds were evaluated for anti-oxidant activity by PCL assay (Photochemiluminescence) and for its stability in different solutions and formulations by HPLC. VPP and V were also evaluated on HaCaT cells by proliferation assays

Evaluation of antiradical activity of different cocoa and chocolate products, relation with lipid and protein composition.

Chocolate antioxidant properties are often claimed; however, they are frequently different from the parent natural sources due to the industry or artisan transformation. In particular, antioxidant property of chocolate and cocoa are not adequately taken into consideration by consumers who normally make use of this food just for its flavor and taste properties. In this study, we have investigated the antioxidant capacity and total phenolic content of cocoa nibs, cocoa masses, and corresponding chocolate bars with different percentages of cocoa from different origins. The antioxidant capacity of the different samples was measured by two different assays [1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) and ferric reducing antioxidant of potency (FRAP) tests]. The Folin–Ciocalteu reagent was used to assess the total phenolic content. The masses showed a higher antioxidant power than the nibs, and this has been attributed to the fact that in the nibs is still present the lipid part, which will form the cocoa butter. The influence of milk, whey, and soy proteins was also investigated. Our results showed that the extra dark cocoa bar, 100% cocoa chocolate, is the best in terms of total polyphenol content and in terms of antioxidant capacity according to the DPPH and FRAP tests. In addition, the bars of organic dark chocolate 80%, dark Tanzania 80%, and Trinidad 80% products are well performing in all respects. As highlighted by us, the antiradical properties of cocoa products are higher than many antioxidant supplements in tablets

Oxidative stress in Friedriech&apos;s Ataxia patients: effect of tocotrienol supplementation

Friedreich\u2019s Ataxia (FRDA) is characterized by oxidative stress as well as by impaired mitochondrial functions. Patients are currently treated with idebenone, a CoQ10 analogue, and the therapeutic efficacy of Vit. E has been documented. In order to develop a model useful to investigate the efficacy of the approaches for oxidative stress damage protection, a number of biochemical parameters related to oxidative stress were identified and studied in blood samples from five young FRDA patients who assumed tocotrienol (5 mg/kg/day), a highly lipophilic Vit. E analogue, for two months. The following features were studied: white blood cell gene expression of SOD-1, SOD-2, catalase, GPX-1, GSR and GSTM-1; plasma content of GSH and GSSG; amount of plasma hexanoyl-lysine adducts; plasma Oxygen Radical Absorbance Capacity; amount of plasma carbonylated proteins; lipid composition of erythrocyte membranes. Such wide array of different markers consistently pointed to the presence of oxidative stress in FRDA patients, despite the fact that the idebenone therapy had not been discontinued. However, even a two month low-dose tocotrienol supplementation led to the decrease of oxidative stress indexes and to parameter values that approached those of healthy controls. Moreover, there are evidences that a longer tocotrienol treatment may be more effective in reducing oxidative stress

A new integrated biochemical approach shows a dec rease of oxidative stress in idebenone.-treated FRDA patients after oral tocotrienol supplementation

Friedreich\u2019s Ataxia (FRDA) is characterized by oxidative stress as well as by impaired mitochondrial functions. Patients are currently treated with idebenone, a CoQ10 analogue, and the therapeutic efficacy of Vit. E has been documented. In order to develop a model useful to investigate the efficacy of the approaches for oxidative stress damage protection, a number of biochemical parameters related to oxidative stress were identified and studied in blood samples from five young FRDA patients who assumed tocotrienol (5 mg/kg/day), a highly lipophilic Vit. E analogue, for two months. The following features were studied: white blood cell gene expression of SOD-1, SOD-2, catalase, GPX-1, GSR and GSTM-1; plasma content of GSH and GSSG; plasma Oxygen Radical Absorbance Capacity; amount of plasma carbonylated proteins; lipid composition of erythrocyte membranes. Such wide array of different markers consistently pointed to the presence of oxidative stress in FRDA patients, despite the fact that the idebenone therapy had not been discontinued. However, even a two month low-dose tocotrienol supplementation led to the decrease of oxidative stress indexes and to parameter values that approached those of healthy controls. Moreover, there are evidences that a longer tocotrienol treatment may be more effective in reducing oxidative stress

Oxidative Stress and Erythrocyte Membrane Alterations in Children with Autism: Correlation with Clinical Features

It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na+/K+-ATPase activity (-66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-omega 3 with a consequent increase in omega 6/omega 3 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD