Attività antiossidante dei capsinoidi in diversi modelli sperimentali di stress ossidativo.

The fruits of Capsicum annum (sweet pepper) are a good source of natural antioxidants and one of this compound, capsiate the most important capsinoid, is present in great quantity in the fruits of a nonpungent cultivar called CH-19 Sweet. In this work it has been evaluated the antioxidant activity of vanillyl nonanoate, a synthetic analog of natural capsiate, during linoleic acid and cholesterol oxidation, and the LDL-oxidation in presence of Cu2+. In these experimental systems the ability of the compound to inhibit the lipid peroxidation induced by ROO. radicals and its chelating properties has been underlined. Moreover the phenol showed a protective effect in VERO cells against the tBH-induced reduction of the main membrane lipids. The vanillyl nonanoate exerted in vivo an important protective effect on the plasma and kidney lipid fraction of rats in a model of oxidative stress induced by a sub-lethal dose of ferric nitrilotriacetate (FeNTA), showing a more evident protection in the plasma compared to that observed in the kidney. From the obtained results, vanillyl nonanoate showed an interesting antioxidant activity in vitro and in vivo and taking into account that this phenolic compound exhibits the same biological activities of the natural capsiate, it can be considered an attractive antioxidant candidate for human use

Rubinstein-Taybi Syndrome: spectrum of CREBBP mutations in Italian patients

BACKGROUND: Rubinstein-Taybi Syndrome (RSTS, MIM 180849) is a rare congenital disorder characterized by mental and growth retardation, broad and duplicated distal phalanges of thumbs and halluces, facial dysmorphisms and increased risk of tumors. RSTS is caused by chromosomal rearrangements and point mutations in one copy of the CREB-binding protein gene (CREBBP or CBP) in 16p13.3. To date mutations in CREBBP have been reported in 56.6% of RSTS patients and an average figure of 10% has ascribed to deletions. METHODS: Our study is based on the mutation analysis of CREBBP in 31 Italian RSTS patients using segregation analysis of intragenic microsatellites, BAC FISH and direct sequencing of PCR and RT-PCR fragments. RESULTS: We identified a total of five deletions, two of the entire gene and three, all in a mosaic condition, involving either the 5' or the 3' region. By direct sequencing a total of 14 de novo mutations were identified: 10 truncating (5 frameshift and 5 nonsense), one splice site, and three novel missense mutations. Two of the latter affect the HAT domain, while one maps within the conserved nuclear receptor binding of (aa 1–170) and will probably destroy a Nuclear Localization Signal. Identification of the p.Asn1978Ser in the healthy mother of a patient also carrying a de novo frameshift mutation, questions the pathogenetic significance of the missense change reported as recurrent mutation. Thirteen additional polymorphisms, three as of yet unreported, were also detected. CONCLUSION: A high detection rate (61.3%) of mutations is confirmed by this Italian study which also attests one of the highest microdeletion rate (16%) documented so far

New insights into the antioxidant activity and cytotoxicity of arzanol and effect of methylation on its biological properties

The heterodimeric phloroglucinyl pyrone arzanol (Arz) has raised considerable interest because of its antiviral, anti-inflammatory, and antioxidant activity. We have investigated the effect of methylation of the pyrone moiety on the antioxidant activity and cytotoxicity of Arz. This manoeuvre, that left the polyphenolic moiety unscathed, was nevertheless detrimental for antioxidant activity in both the cholesterol thermal degradation- and the Cu2+-induced liposome oxidation assays, providing evidence of structure-activity relationships that go beyond the preservation of the polyphenolic pharmacophore. The antioxidant activity of Arz was retained also in the Fe-NTA model of in vivo oxidative stress, with protective effect on the oxidative degradation of plasmatic lipids, unsaturated fatty acids and cholesterol. Both Arz and methylarzanol (Me-Arz) were devoid of toxic effect on colonic differentiated Caco-2 cells up to 100 μM, but significantly reduced cancer Caco-2 cell viability at lower dosages. Arz could also selectively reduce viability of other cancer cell lines, [murine melanoma cells (B16F10 cells), human cervical carcinoma cells (HeLa cells)], suggesting that it can act as a selective modulator of cell processes typical of cancer cells. Taken together, our results qualify Arz as a lead structure for further in vivo investigation of its pharmacological potential

Potential anti-tumor effects of Mugil cephalus processed roe extracts on colon cancer cells

The salted-semidried mullet ovary product, bottarga, is a Mediterranean food rich in n-3 PUFA EPA and DHA. We studied and compared the effects on cell viability, sensitivity to the anti-tumor drug 5-fluorouracil, and lipid composition, in colon cancer Caco-2 cells after 24 h incubation with oils and hydrophilic extracts obtained from two bottarga samples stored at different conditions. The cellular absorption of bottarga lipids was assessed in cancer cells by the evaluation of lipid accumulation in cytoplasmic lipid droplets by fluorescence microscopy. Bottarga oil showed a significant in vitro inhibitory effect on the growth of cancer Caco-2 cells and the ability to potentiate, at non-toxic concentration, the growth inhibitory effect of 5-fluorouracil. Moreover, bottarga oil induced in cancer Caco-2 cells marked changes in fatty acid composition, with a significant accumulation of the n-3 PUFA EPA and DHA, and cytoplasmic lipid droplet formation. Also bottarga hydrophilic extract, characterized by means of 1H NMR spectroscopy, exhibited a reduction in cancer cell viability, without affecting cell lipid profile. Cell cholesterol levels were unmodified by all treatments. The results showed interesting anti-tumor properties of bottarga lipids, and qualify this fish product as a food with nutraceutical properties and potential benefits in colon cancer prevention

Multivariate fatty acid and fatty alcohol profile of mullet bottarga

Mullet bottarga is a food delicacy obtained by salting and drying the intact roes of mullet (Mugil spp.). The fatty acid and fatty alcohol compositions of different samples of bottarga were studied by means of gas chromatography (GC) and multivariate analysis (MVA). High percentages of beneficial n-3 PUFA, among which docosahexaenoic acid (DHA) (22:6n-3, 11.9%) and eicosapentaenoic acid (EPA) (20:5n-3, 8.6%), were detected. Differences in the concentrations of unsaturated FA and FAL were observed among samples, while saturated components showed little variations. On the other hand, the total contents of saturated, monounsaturated and polyunsaturated components were similar. The principal component analysis loadings bi-plot showed that n-6 PUFA concentrations were inversely correlated to those of n-3 PUFA, except for DHA that showed no correlations. Correlations between FAL concentrations were also observed. Furthermore, integrating our GC data with those from the literature on mullet and tuna bottarga, the MVA showed that both bottarga typologies exhibit a similar trend in the FA distribution and that 16:0 and 16:1n-7 FA are the variables with the highest discriminant power. In this work, we demonstrated the usefulness of the application of MVA to GC data to extract meaningful information otherwise hidden in the amount of data

Antioxidant properties of extracts and compounds from Psoralea Morisiana

The antioxidant activity of various extracts (MeOH, petroleum ether, EtOAc) from the aerial parts of Psoralea morisiana, an endemic Sardinian plant, was evaluated during autoxidation and iron-mediated oxidation of linoleic acid at 37°C and during cholesterol oxidation at 140°C, in the absence of solvent. The activity of erybraedin C, bitucarpin A and plicatin B, isolated from the extracts, was investigated under the same experimental conditions and compared to that of BHT and α-tocopherol. All the extracts, erybraedin C (major constituent of the extracts) and plicatin B showed powerful antioxidant properties. None of the extracts and pure compounds showed any prooxidant activity. The cytotoxicity of the extracts, erybraedin C, and plicatin B was further evaluated in VERO cells, a line of fibroblasts derived from monkey kidney. Erybraedin C, at non-cytotoxic concentrations, showed a strong inhibition of FeCl3-induced oxidation in VERO cell

Cholesterol as target of Fe-NTA-induced lipid peroxidation in rat tissues

Abstract Intraperitoneal injection of the iron-chelate, ferric-nitrilotriacetate (Fe-NTA), induces renal proximal tubular damage associated with oxidative damage in vivo. A sub-lethal dose of Fe-NTA (15 mg Fe/kg body weight) was administered IP to rats; animals were sacrificed and liver, kidney and plasma were collected 1-4 h after injection. In response to the Fe-NTA administration, there were significant time-dependent reductions of the levels of total lipids, cholesterol and total unsaturated fatty acids, and a rise in the concentrations of conjugated dienes, 7-ketocholesterol and fatty acids hydroperoxides, showing a pattern inversely correlated in plasma, kidney and liver. Cholesterol level decreased significantly from 1 h after injection in the kidney and 3-4 h in the plasma and liver of treated rats. This is the first report on cholesterol reduction and accumulated 7-ketocholesterol in the tissues of rats treated with Fe-NTA as a consequence of lipid peroxidation