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To exploit the full potential of pomegranate marcs, this study explores different conditions of ‘green’ extraction of ellagitannins and other bio-active phenolic compounds from the ‘external by-product’ of pomegranate industrial processing. Significant recoveries of ellagitannins, free ellagic acid and radical scavenging compounds were obtained by coupling both the traditional (MH) or the hydro-diffusion gravity (MHG) microwave assisted drying to a direct ultrasound assisted extraction (UAE) using a food-grade solvent (EtOH/H2O). The amounts of the ellagitannins after microwave drying were always significantly higher than with the traditional oven drying. Moreover, microwaves reduced the drying times from several hours to few minutes reaching comparable residual moisture content. The microwave hydro-diffusion gravity system allowed the recovery of bio-active compounds in the condensed water too. The comparison of UAE with traditional maceration and decoction highlighted the higher efficiency of UAE in the quicker extraction of bio-active compounds, except for the total ellagitannins which were better recovered after the longer maceration.

Drugs delivered by proper carriers enter into the cells much more rapidly and carry out their action much more promptly than in the free forms. A high drug concentration can be sustained for longer periods of time at the target site in the cell. In in vivo conditions, this would translate into a reduction of systemic toxicity, dosage and frequency of dosing. Dendritic polymers significantly affect drug delivery in terms of reaching the target site, modifying the bio-distribution of the drug, and enhancing the efficacy of different drugs including anticancer compounds. 2-({[2-({[(2-tolyl)amino]carbonothioyl}oxy)ethyl]amino}carbo-nyl)benzoic acid 1 is a thiocarbamate derivative belonging to an already reported class of non-nucleoside HIV-1 reverse transcriptase inhibitors. In in vitro assay it showed no cytotoxic effects but was endowed with very low solubility and poor activity against wild-type HIV-1 (EC50 = 27 μM). With the aim at improving its water solubility, 1 has been successfully incorporated inside non-toxic amino acids-modified core-shell hetero dendrimers. IR, NMR, zeta potential, mean size of particles, buffer capacity and in vitro release profile of prepared materials were reported. All dendriplexes were evaluated in cell-based assays to assess their cytotoxic profile. The obtained complexes, which harmonize a peripheral polycationic character and a buffer capacity which presuppose efficient cells penetration and increased residence time with a not PAMAM structured biodegradable scaffold, were well water-soluble and could rationally appear as a promising set of prodrugs for safe in vivo administrations.

Dendrimers are macromolecules characterized by high controlled size, shape and architecture, presence of inner cavities able to accommodate small molecules and many peripheral functional groups to bind target entities. They are of eminent interest for biomedical applications, including gene transfection, tissue engineering, imaging, and drug delivery. The well-known pharmacological activities of ursolic and oleanolic acids are limited by their small water solubility, non-specific cell distribution, low bioavailability, poor pharmacokinetics, and their direct administration could result in the release of thrombi. To overcome such problems, in this paper we described their physical incorporation inside amino acids-modified polyester-based dendrimers which made them highly water-soluble. IR, NMR, zeta potential, mean size of particles, buffer capacity and drug release profiles of prepared materials were reported. The achieved water-soluble complexes harmonize a polycationic character and a buffer capacity which presuppose efficient cell penetration and increased residence time with a biodegradable cell respectful scaffold, thus appearing as a promising team of not toxic prodrugs for safe administration of ursolic and oleanolic acids.

International audience; Oryza sativa L. 'Violet Nori' is an Italian cultivar of spontaneous growing aromatic purple rice which is particularly rich in polyphenolic compounds, especially anthocyanins, conferring it an excellent antioxidant capacity. The present study aimed at increasing the extraction yields of its antioxidant compounds with green strategies and it is divided into two steps. The first step concerned a solubility study of the targeted polyphenols in different ethanol:water mixtures by means of a theoretical prediction method, using the simulation program COSMO-RS, and the subsequently confirmation of the computational results by practical experiments. Once the best extraction mixture was identified, the second step of the work was performed, with the purpose of intensifying the extraction yield. Therefore, various innovative green extraction techniques, including ultrasound, using both the probe system and the ultrasonic bath, bead milling, microwave and accelerated solvent extractions were tested and compared to conventional maceration.Results, expressed in terms of total phenolic and total monomeric anthocyanin contents, showed that the best extracting solvent for 'Violet Nori' rice was the mixture ethanol:water (60:40 v/v), being COSMO-RS computational predictions in good correlation with the experimental results. Moreover, the most efficient techniques to extract the antioxidant compounds resulted to be both ultrasound-assisted extraction probe and bead milling, that in only 5 min got the same extractive efficiency obtained after 3 h of conventional maceration.

Pomegranate fruit is recognized as an important source of health compounds and its juicy arils represent the most commercially exploitable part of the fruit. Nevertheless, by-products coming from pomegranate juice processing represent both a challenging disposal problem and a promising source of health ingredients. In particular, the marcs obtained after juice squeezing are usually discarded or used for oil production in virtue of their lipophilic fraction, although the residues of pericarp and arils are proven to still be a good source of hydrophilic compounds such as polyphenols. Pulsed ultrasound-assisted extraction, using just water as solvent, and spray-drying microdispersion, using low methoxyl pectin as polymeric matrix, have been employed, respectively, to extract and formulate the water-soluble bioactive molecules from these by-products. From 100 g of pomegranate fresh marcs, almost the same quantity of phenolic compounds found in 100 mL of the corresponding juice can be extracted with similar antioxidant activity, but with higher content in vitamin C and practically without total soluble solids. The extracts have been sprayed obtaining powders with an encapsulation efficiency of about 50%. The extracts, both before and after the microparticles production, have been characterized and their capacity in inhibition of platelets aggregation induced by thrombin has been tested ex vivo on human platelets (% inhibition: about 60% and 30% before and after microencapsulation, respectively). Finally, fresh-cut apple wedges were enriched by vacuum impregnation with the formulated extracts, tentatively used as potential novel ingredients, obtaining “polyphenol-enriched” apples.

It is well known that several polycyclic aromatic hydrocarbons (PAHs), products of incomplete pyrolysis of organic material, have proved to be extremely toxic to humans. Food can be contaminated by these compounds in many different ways and diet represents nowadays the major source of exposure to PAHs for non-smokers population. In the present study, three of the most important carcinogenic PAHs in foods, according to the legislation currently in force, i.e. benzo[a]pyrene (BaP), benzo[a]anthracene (BaA) and chrysene (Chry), were firstly arranged in ternary mixtures, following an experimental design. Then, an organic extraction from a commercial smoked tuna, potentially affected by PAHs, was performed to investigate the presence of the three compounds under study. A spectrofluorimetric method based on the second order calibration of excitation-emission fluorescence matrices (EEMs) and parallel factor analysis (PARAFAC) decomposition was proposed in this work as analytical approach for PAHs detection. Both in the ternary mixtures and in the food matrix (smoked tuna), PAHs were unequivocally identified and quantified with decision limit (CCα) and capability of detection (CCβ) equal to 0.11 µg L−1 and 0.21 µg L−1 for BaP, 0.27 µg L−1 and 0.53 µg L−1 for BaA and 0.18 µg L−1 and 0.35 µg L−1 for Chry, respectively, when the probabilities of false positive (α) and false negative (β) were fixed at 0.05. In the investigated smoked tuna, detectable levels of BaP were found, whereas BaA and Chry were absent., MINECO (AEI/FEDER, UE) and Junta de Castilla y León through projects CTQ2017-88,894-R and BU012P17 respectively (all co-financed with FEDER funds).

Natural polyphenols such as Gallic Acid (GA) form an important class of bioactive chemical entities that, having innumerable biological properties, could represent a safer alternative to common drugs against several disorders, including platelet aggregation, radical oxygen species (ROS) hyperproduction, oxidative stress (OS) and bacterial infections. Unfortunately, their clinical uses are limited by pharmacokinetics drawbacks and high sensitivity to environmental factors. In order to overcome these problems and to exploit the GA curative potentials, it has been linked to a biodegradable nanospherical dendrimer matrix, capable of protecting it, thus obtaining a GA-enriched nanosized dendrimer (GAD) endowed with a strong antioxidant capacity. GAD activity as an inhibitor of platelet aggregation and ROS accumulation and its antibacterial efficiency are evaluated here and compared to those of free GA, obtaining outcomes never achieved. Regarding platelet aggregation induced by thrombin and collagen, the GAD proved to be stronger by 7.1 and 7.3 times, respectively. Furthermore, the GAD showed a ROS inhibitory activity higher than that of GA by 8.1 (thrombin) and 6.9 (collagen) times. Concerning the antibacterial activities, evaluated on eleven multi-resistant Gram-positive strains of clinical relevance, the GAD is far more potent than GA, by exerting a growth inhibitory activity at MIC (μM) concentrations lower by factors in the range 12–50.

Ellagic acid (EA) is a bioactive natural polyphenol with antioxidant and several other beneficial properties, but unfortunately it cannot be exploited for in vivo therapeutic applications because of its poor water solubility and accordingly low bioavailability. Aiming to increase EA solubility, an EA solid microdispersion was realized by employing only water and low methoxylated pectin as a food compatible excipient by applying spray drying technology. It showed a 22% (w/w) Drug Loading (DL), a 30 times improved water solubility and remarkable radical scavenging activity. Subsequently, adopting non-PAMAM hydrophilic and amphiphilic dendrimers as nanocontainers, two EA nanodispersions were achieved (60–70 nm) with 46 and 53% (w/w) DL, water solubility 300 to 1000 times higher than that of free EA and good antioxidant capability. In both cases, toxic agents such as castor oil, Tween 80 or the extensively used but not so safe PEG400 were avoided and no previously used carriers, including β-cyclodextrins, were adopted. The prepared micro- and nanodispersions showed water solubility never obtained before and represent non-toxic EA reservoirs suitable for food and biomedical applications.

The study is focused on the effect of different cooking conditions on the antioxidant content, particularly anthocyanins, of Oryza sativa L. ‘Violet Nori’, a new black rice cultivar. 10 different cooking tests were performed. The selected cooking conditions allowed to evaluate the effect of boiling, roasting, oven cooking, risotto cooking, and oriental cooking. The total anthocyanins amounts were evaluated by both a spectrophotometric pH differential method and High-Performance Liquid Chromatography (HPLC), together with the Total Phenolic Content (TPC) and the Radical Scavenging Activity (RSA). The obtained results showed that boiling with a low water amount (100 g rice/650 mL water) and oriental cooking, which allows a reduction of boiling times thanks to the lid of the pot, allow effectively saving at least part of their anthocyanins content. Similar results were obtained by boiling if rice was introduced in cold or boiling water, but on the contrary a ratio of 100 g rice/1000 mL water greatly enhanced the loss of antioxidant compounds. Risotto and oven cooking allowed obtaining results that were roughly intermediate between the ‘best’ and the ‘worst’ results. A high correlation existed between the amounts of total anthocyanins and both TPCs and RSAs. The ‘best’ results show that although cooking necessarily decreases the rice content of valuable antioxidants, a careful choice of the operative conditions allows effectively preserving amounts of total anthocyanins higher than 100 mg/100 g rice portion, which are close to or even higher than in other well-known sources of dietetic anthocyanins.

It is well-known that the health properties attributed to several fruits, herbs, seeds and their processed foods/beverages are due to an important group of natural polyphenols classified as hydrolysable tannins (HT) named ellagitannins (ETs), that encompass both one or more gallic acid (GA) units and one or more hexahydroxydiphenoic acid (HHDP) units, ester-connected with a sugar residue. In vivo, ETs are rather not absorbed and in gastrointestinal tract (GIT), they are hydrolysed providing mainly ellagic acid (EA). Due to its trivial water-solubility, first pass effect, metabolism in GIT, or irreversible binding to cellular DNA and proteins, EA has a very low bioavailability. Some authors are studying methods to increase EA water-solubility and thus to improve its bioavailability. At the same, EA metabolism to urolithins (UROs), whose concentration and activity is inter-individual and intra-individual dependent, is still under study and not completely elucidate. Numerous in vitro and in vivo studies have been carried out to define the molecular and cellular events underlying the beneficial effects that this compound and its metabolites exert in pathological conditions. The anti-inflammatory and the antioxidant properties of EA attracted the interest of researchers for its potential health benefits in humans, including anti-cancer, anti-diabetes activities and cardio-protection. Nevertheless, lately the attention paid to EA is focusing on its potential protective action towards several neurodegenerative disorders. Thus, EA is investigated as a potential “lead compound” endowed with multi-target pharmacological properties on CNS. Since the identification of the pharmacophore(s) responsible for both health benefits and collateral effects of this compound is crucial in drug discovery, this review aims to provide an all-round updated analysis of the literature concerning EA involvement in several CNS disorders, hoping that such information will be useful to researchers involved in multi-target drug design for CNS.

Even though the idea that amyloid β peptide accumulation is the primary event in the pathogenesis of Alzheimer's disease has become the leading hypothesis, the causal link between aberrant amyloid precursor protein processing and tau alterations in this type of dementia remains controversial. We further investigated the role of β-amyloid production/deposition in tau pathology and neuronal cell death in the mouse brain by crossing Tg2576 and VLW lines expressing human mutant amyloid precursor protein and human mutant tau, respectively. The resulting double transgenic mice showed enhanced amyloid deposition accompanied by neurofibrillary degeneration and overt neuronal loss in selectively vulnerable brain limbic areas. These findings challenge the idea that tau pathology in Alzheimer's disease is merely a downstream effect of amyloid production/deposition and suggest that reciprocal interactions between β-amyloid and tau alterations may take place in vivo., This project was funded in part by EC grant DIADEM QRLT-2000-026362, SAF2004-07802 and UTE project CIMA

In addition to genetic factors, environmental factors have long been suspected to contribute to the pathogenesis of Parkinson's disease (PD). We investigated the possible interaction between genetic factors and neurotoxins by testing whether alpha-synuclein A30P Tg5093 transgenic mice show increased sensitivity to secondary toxic insults like 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or rotenone. While sensitivity to chronic treatment with rotenone was not enhanced in the Tg5093 line, chronic treatment with 80 or 150 mg/kg MPTP resulted in increased deterioration of the nigrostriatal dopaminergic system as assessed by quantitation of nigral tyrosine hydroxylase (TH) positive neurons and striatal dopamine (DA) levels in Tg5093 mice when compared to non-transgenic littermate controls. Thus, the results of this study demonstrate a role for the overexpression of mutant human alpha-synuclein A30P in increased vulnerability of DA neurons to MPTP.