2,272 research outputs found
Purification of euphorbia characias latex peroxidase by calmodulin-affinity chromatography
No full textSynthesis and biological activity of 2-phenylbenzofuran derivatives as butyrylcholinerase inhibitors
No full textAlzheimer disease (AD) is an irreversible and progressive brain disorder characterized by progressive memory loss and a wide range of cognitive impairments. An accepted strategy towards its treatment is to restore the levels of acetylcholine by inhibiting cholinesterase enzymes, such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). BChE activity progressively increases in patients with AD, while AChE activity remains unchanged or declines, with changes that become more and more pronounced during the disease course. Therefore, compounds that selectively interact with BChE might have a relevant role in treatment of patients with advanced AD.
Benzofuran scaffold has drawn considerable attention over the last few years due to its profound physiological and chemotherapeutic properties. In our recent study, a series of 2-phenylbezonfurans compounds were synthesized and their inhibition activity towards both the enzymes were investigated. These compounds showed no inhibition toward AChE while inhibited BChE with different efficiencies. In addition to biological assays, molecular dynamics simulations allowed highlighting the molecular basis of the selective BChE inhibition by the benzofuran scaffold.
Based on these previous results, in the current work we have designed new 2-benzofurans derivatives in order to increase the strength of enzyme inhibition. We have used the Wittig reaction as a key step of a good methodology for the efficient and general synthesis of a selected series of 2-phenylbenzofurans. For all the compounds of the series, the IC50 values were determined.
In this scenario, our findings could be extended to design and develop new potentially therapeutic molecules, especially useful in neurodegenerative diseases
Nutrient availability links mitochondria, apoptosis, and obesity
No full textMitochondria are the dominant source of the cellular energy requirements through oxidative phosphorylation, but they are also central players in apoptosis. Nutrient availability may have been the main evolutionary driving force behind these opposite mitochondrial functions: production of energy to sustain life and release of apoptotic proteins to trigger cell death. Here, we explore the link between nutrients, mitochondria and apoptosis with known and potential implications for age‐related decline and metabolic syndromes
Tempranillo grape extract in transfersomes: A nanoproduct with antioxidant activity
No full textPolyphenols are gaining increasing interest due to their beneficial properties to human health. Grape pomace, the by-product of wine production, is a source of these bioactive compounds. An extract from Tempranillo grape pomace was obtained and characterized qualitatively and quantitatively. The major components found were anthocyanins, flavan-3-ols, and flavonols. To improve the bioavailability of these compounds, the extract was formulated in phospholipid vesicles, namely transfersomes. Spherical unilamellar vesicles around 100 nm each were obtained. The antioxidant activity of both the extract and the transfersomes was evaluated by using colorimetric assays (i.e., DPPH, FRAP, and Folin–Ciocalteu). The cells’ viability and the antioxidant activity were assessed in keratinocytes. The results showed that the extract and the transfersomes had no cytotoxic effects and exerted remarkable antioxidant activity, which was more evident in a vesicle formulation. These findings highlighted the potential of the Tempranillo grape pomace extract and the efficacy of the incorporation into phospholipid vesicles.Fil: Asensio Regalado, Carlos. Universidad del País Vasco; EspañaFil: Alonso Salces, Rosa Maria. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; ArgentinaFil: Gallo, Blanca. Universidad del País Vasco; EspañaFil: Berrueta, Luis A.. Universidad del País Vasco; EspañaFil: Era, Benedetta. Università Degli Studi Di Cagliari.; ItaliaFil: Pintus, Francesca. Università Degli Studi Di Cagliari.; ItaliaFil: Caddeo, Carla. Università Degli Studi Di Cagliari.; Itali
Antityrosinase activity of Euphorbia characias extracts
No full textTyrosinase is a well-known key enzyme in melanin biosynthesis and its inhibitors have become increasingly important because of their potential use as hypopigmenting agents. In the present study, the anti-melanogenic effect of aqueous and ethanolic extracts from Euphorbia characias leaves, stems, and flowers in cell-free and cellular systems was examined. All the extracts showed inhibitory effects against mushroom tyrosinase with leaf extracts exhibiting the lowest IC50 values of 24 and 97 μg/mL for aqueous and ethanolic extracts respectively. Enzyme kinetic analysis indicated that leaf aqueous extract acts as a mixed type inhibitor, while ethanolic extract shows a competitive inhibition effect on mushroom tyrosinase using L-DOPA as substrate. In addition, the inhibitory effect of leaf extracts on tyrosinase activity and melanin production was examined in murine melanoma B16F10 cells. Cellular tyrosinase activity as well as levels of melanin synthesis are reduced in a dose-dependent manner by extracts in cells treated with α-melanocyte stimulating hormone (α-MSH). The effects are comparable, and sometimes even better, than that of kojic acid, a well known tyrosinase inhibitor used for reference. All these results suggest that E. characias could be a great source of the natural inhibitors from tyrosinase and has the potential to be used as a whitening agent in therapeutic fields
Bioseparation of Four Proteins from Euphorbia characias Latex: Amine Oxidase, Peroxidase, Nucleotide Pyrophosphatase/Phosphodiesterase, and Purple Acid Phosphatase
No full textThis paper deals with the purification of four proteins from Euphorbia characias latex, a copper amine oxidase, a nucleotide pyrophosphatase/phosphodiesterase, a peroxidase, and a purple acid phosphatase. These proteins, very different in molecular weight, in primary structure, and in the catalyzed reaction, are purified using identical preliminary steps of purification and by chromatographic methods. In particular, the DEAE-cellulose chromatography is used as a useful purification step for all the four enzymes. The purification methods here reported allow to obtain a high purification of all the four proteins with a good yield. This paper will give some thorough suggestions for researchers busy in separation of macromolecules from different sources
Recommendations of the Sardinian public for the treatment of depression
No full textBackground: Public beliefs about appropriate treatment impact, help-seeking and treatment adherence.Aim: To determine the recommendations of the Sardinian public for the treatment of depression.Methods: In 2012, a population-based survey was conducted by phone in Sardinia (N = 1,200). In the context of a fully structured interview, respondents were presented with a vignette depicting a case of depression. Subsequently, they were asked about their treatment recommendations. The results are contrasted with findings from a similar survey which had been conducted in Vienna 3 years before.Results: In Sardinia as in Vienna, psychotherapy was the uncontested favorite, while antidepressant medication was recommended by relatively few respondents. In Sardinia, there were also no marked differences between urban and rural areas with regard to these two treatments. However, between Sardinia and Vienna, as well as within Sardinia, great differences were found with regard to autogenic training and ?alternative? methods like homeopathic medicines and acupuncture.Conclusion: Cross-cultural comparisons may help better understand treatment preferences of the public. In Sardinia, as in Vienna, there seems to be a need for improving the public?s knowledge about the appropriate treatment of depression
Allosteric modulation of Euphorbia peroxidase by nickel ions
No full textA class III peroxidase, isolated and characterized from the latex of the
perennial Mediterranean shrub Euphorbia characias, contains one ferric
iron–protoporphyrin IX pentacoordinated with a histidine ‘proximal’
ligand as heme prosthetic group. In addition, the purified peroxidase contained
1 mole of endogenous Ca2+ per mole of enzyme, and in the presence
of excess Ca2+, the catalytic efficiency was enhanced by three orders
of magnitude. The incubation of the native enzyme with Ni2+ causes
reversible inhibition, whereas, in the presence of excess Ca2+, Ni2+ leads
to an increase of the catalytic activity of Euphorbia peroxidase. UV⁄ visible
absorption spectra show that the heme iron remains in a quantum mechanically
mixed-spin state as in the native enzyme after addition of Ni2+, and
only minor changes in the secondary or tertiary structure of the protein
could be detected by fluorescence or CD measurements in the presence of
Ni2+. In the presence of H2O2 and in the absence of a reducing agent,
Ni2+ decreases the catalase-like activity of Euphorbia peroxidase and accelerates
another pathway in which the inactive stable species accumulates
with a shoulder at 619 nm. Analysis of the kinetic measurements suggests
that Ni2+ affects the H2O2-binding site and inhibits the formation of compound
I. In the presence of excess Ca2+, Ni2+ accelerates the reduction of
compound I to the native enzyme. The reported results are compatible with
the hypothesis that ELP has two Ni2+-binding sites with opposite functional
effects
Amine oxidase from Euphorbia characias: kinetic and structural characterization
No full textThis minireview focuses on a plant copper/2,4,5-trihydroxyphenyl alanine quinone amine oxidase isolated from the latex of the shrub Euphorbia characias (ELAO). This enzyme has been investigated in terms of both molecular structure and kinetic mechanism. The characterization of this enzyme allowed us to identify specific amino acids and domains that play a key role in modulating substrate access into the active site not only for ELAO but also for other plant and mammalian amine oxidases. As mammalian amine oxidases are implicated in several physiological and pathological conditions, the deep structural characterization of their active site accession mechanisms could be the starting point for the development of enzyme modulators with high therapeutic potential. Thus, this paper gives tructural/functional insights that open new perspectives in the research about the whole amine oxidase family
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