Melatonin and phytomelatonin: Chemistry, biosynthesis, metabolism, distribution and bioactivity in plants and animals—an overview

Melatonin is a ubiquitous indolamine, largely investigated for its key role in the regulation of several physiological processes in both animals and plants. In the last century, it was reported that this molecule may be produced in high concentrations by several species belonging to the plant kingdom and stored in specialized tissues. In this review, the main information related to the chemistry of melatonin and its metabolism has been summarized. Furthermore, the biosynthetic pathway characteristics of animal and plant cells have been compared, and the main differences between the two systems highlighted. Additionally, in order to investigate the distribution of this indolamine in the plan…

Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells.

Dietary redox-active/antioxidant phytochemicals may help control or mitigate the inflammatory response in chronic inflammatory bowel disease (IBD). In the present study, the anti-inflammatory activity of indicaxanthin (Ind), a pigment from the edible fruit of cactus pear (Opuntia ficus-indica, L.), was shown in an IBD model consisting of a human intestinal epithelial cell line (Caco-2 cells) stimulated by IL-1β, a cytokine known to play a major role in the initiation and amplification of inflammatory activity in IBD. The exposure of Caco-2 cells to IL-1β brought about the activation of NADPH oxidase (NOX-1) and the generation of reactive oxygen species (ROS) to activate intracellular signal…

Improvement of Fatty Acid Profile in Durum Wheat Breads Supplemented with Portulaca oleracea L. Quality Traits of Purslane-Fortified Bread

The addition of functional ingredients to breads could have effects on preventing cardiovascular diseases, cancers and inflammation. The incorporation of 0&ndash

Antioxidant activity of Sicilian Pistachio (Pistacia vera, L. var. Bronte) nut extracts and its bioactive components

Pistacia vera L. is the only species of Pistacia genus producing edible nuts. This paper investigates the antioxidant potential of a Sicilian variety of pistachio nut by chemical as well as biological assays and measured antioxidant vitamins and a number of antioxidant polyphenols in either the hydrophilic and/or the lipophilic nut extract. In accordance with the majority of foods, the total antioxidant activity, measured as a TAA test, was much higher (50-fold) in the hydrophilic than in the lipophilic extract. Substantial amounts of total phenols were measured. The hydrophilic extract inhibited dose- dependently both the metal-dependent and -independent lipid oxidation of bovine liver mic…

Antioxidant activity of sicilian caper (Capparis spinosa L.) and its bioactive compounds

Kinetics of the lipoperoxyl radical-scavenging activity of indicaxanthin in solution and unilamellar liposomes

Abstract The reaction of the phytochemical indicaxanthin with lipoperoxyl radicals generated in methyl linoleate methanol solution by 2,20-azobis(2,4-dimethylvaleronitrile), and in aqueous soybean phosphatidylcholine unilamellar liposomes by 2,20-azobis(2- amidinopropane)hydrochloride, was studied. The molecule acts as a chain-terminating lipoperoxyl radical scavenger in solution, with a calculated inhibition constant of 3.63 £ 105M21 s21, and a stoichiometric factor approaching 2. Indicaxanthin incorporated in liposomes prevented lipid oxidation, inducing clear-cut lag periods and decrease of the propagation rate. Both effects were concentration-dependent, but not linearly related to the p…

Raman Spectroscopic Measurements of Dermal Carotenoids in Breast Cancer Operated Patients Provide Evidence for the Positive Impact of a Dietary Regimen Rich in Fruit and Vegetables on Body Oxidative Stress and BC Prognostic Anthropometric Parameters: A Five-Year Study

Dermal carotenoids are a feasible marker of the body antioxidative network and may reveal a moderate to severe imbalance of the redox status, thereby providing indication of individual oxidative stress. In this work noninvasive Resonance Raman Spectroscopy (RRS) measurements of skin carotenoids (skin carotenoid score (SCS)) were used to provide indications of individual oxidative stress, each year for five years, in 71 breast cancer (BC) patients at high risk of recurrence. Patients’ SCS has been correlated with parameters relevant to BC risk, waist circumference (WC), and body mass index (BMI), in the aim of monitoring the effect of a dietary regimen intended to positively affect BC risk f…

In silico identification of small molecules as new cdc25 inhibitors through the correlation between chemosensitivity and protein expression pattern

The cell division cycle 25 (Cdc25) protein family plays a crucial role in controlling cell proliferation, making it an excellent target for cancer therapy. In this work, a set of small molecules were identified as Cdc25 modulators by applying a mixed ligand-structure-based approach and taking advantage of the correlation between the chemosensitivity of selected structures and the protein expression pattern of the proposed target. In the first step of the in silico protocol, a set of molecules acting as Cdc25 inhibitors were identified through a new ligand-based protocol and the evaluation of a large database of molecular structures. Subsequently, induced-fit docking (IFD) studies allowed us…

DRUDIT: Web-based DRUgs DIscovery Tools to design small molecules as modulators of biological targets

Abstract Motivation New in silico tools to predict biological affinities for input structures are presented. The tools are implemented in the DRUDIT (DRUgs DIscovery Tools) web service. The DRUDIT biological finder module is based on molecular descriptors that are calculated by the MOLDESTO (MOLecular DEScriptors TOol) software module developed by the same authors, which is able to calculate more than one thousand molecular descriptors. At this stage, DRUDIT includes 250 biological targets, but new external targets can be added. This feature extends the application scope of DRUDIT to several fields. Moreover, two more functions are implemented: the multi- and on/off-target tasks. These tool…

Phytochemical profile and antioxidative properties of Plinia trunciflora fruits: A new source of nutraceuticals.

Abstract This study evaluated the polyphenol profile and the antioxidative properties of Plinia trunciflora (O. Berg) Kausel fruits. Folin-Ciocalteau and pH-jumping methods indicated that these berries are a major source of antioxidant polyphenols (1201.05 mg GAE/100 g FW), particularly anthocyanins. HPLC-DAD-ESI-MS/MS analysis identified cyanidine glycosides as the main components. Flavon-3-ols and hydrolysable-tannins were also found. CAA assay showed that extracts of P. trunciflora fruits prevent lipid peroxidation in HepG2 cells with higher efficacy than other colourful fruits (CAA50 935.25 mg FW/mL cell medium). Moreover, our results suggested that the observed antioxidant protection i…

Anti-inflammatory effects of sicilian pistachio (pistacia vera l.) Nut in an in vitro model of human intestinal epithelium

Intestinal epithelial cells play an important role in the mucosal inflammatory response. These cells synthesize and secrete inflammatory mediators, and selectively modulate the permeability of the epithelial monolayer thus exposing immune cells to antigens. Although intestinal inflammatory response is crucial to maintain gut structural integrity and function, alteration and dysregulation of inflammatory pathways contribute to tissue damage and ulceration, and are thought to be pivotal factors in the pathogenesis of different inflammatory gut diseases [1]. The limited efficacy of conventional pharmacological therapy in the intestinal inflammatory conditions has fostered research on alternati…

Chemical–physical characteristics, polyphenolic content and total antioxidant activity of three Italian-grown pomegranate cultivars

Background: In Mediterranean countries, there is an increasing demand for pomegranate fruits due to their antioxidant properties and nutritional values. The large diffusion of new genotypes and cultivars requires the knowledge of all fruit characteristics in connection with the cultivation area, to satisfy the market demand. This study seeks to determine the fruit quality attributes and nutraceutical values of three pomegranate cultivars (Wonderful, Acco and Kamel) grown in the Mediterranean climate. Methods: The fruits were evaluated for their main physico-chemical traits (weight, volume, height, width, thickness, total arils number, total arils weight, juiciness, fruit index, peel index a…

Identification of biological targets through the correlation between cell line chemosensitivity and protein expression pattern.

Matching biological data sequences is one of the most interesting ways to discover new bioactive compounds. In particular, matching cell chemosensitivity with a protein expression profile can be a useful approach to predict the activity of compounds against definite biological targets. In this review, we discuss this correlation. First, we analyze case studies in which some known drugs, acting on known targets, show a good correlation between their antiproliferative activities and protein expression when a large panel of tumor cells is considered. Then, we highlight how the application of in silico methods based on the correlation between cell line chemosensitivity and gene/protein expressi…

Effects of gellan-based coating application on litchi fruit quality traits

The use of gellan-based coating formulation on litchi (Litchi chinensis Sonn. ‘Wai Chee’) fruit was investigated in order to determine its ability to improve color conservation and to maintain the overall quality. Fruits were treated with gellanbased coating (0.5% w/v) and glycerol (3% w/v) after dipping in ascorbic acid (1.5% w/v) and then stored at 5°C and 90% relative humidity for 15 days. Changes in peel color, soluble solid content, tritatable acidity, weight loss, antioxidant activity and phenolic content, were measured. Formulations containing gellan-based coating exhibited slightly improved water barrier properties and showed their active role in maintaining color characteristics an…

Yield, pomological characteristics, bioactive compounds and antioxidant activity of Annona cherimola Mill. grown in mediterranean climate

The agronomic and qualitative responses of the cherimoya (Annona cherimola Mill.) fruit grown in Mediterranean climate are not properly studied. Fruits of Fino de Jete, the most diffused worldwide cultivar of cherimoya, and Torre 1 a new genotype obtained by breeding program in Sicily, Italy, were collected at commercial ripening and subjected to productive (yield efficiency, number of fruits, crop load), analytical (fruit weight, transversal diameter, longitudinal diameter, total soluble solid content, titratable acidity, seed weight, seed number, peel and pulp weight, pulp/seed ratio and colorimetric analysis), bioactive compound content (total antioxidant activity, Phenolic and Carotenoi…

Drugs Polypharmacology by in Silico Methods: New Opportunities in Drug Discovery

Background Polypharmacology, defined as the modulation of multiple proteins rather than a single target to achieve a desired therapeutic effect, has been gaining increasing attention since 1990s, when industries had to withdraw several drugs due to their adverse effects, leading to permanent injuries or death, with multi-billiondollar legal damages. Therefore, if up to then the "one drug one target" paradigm had seen many researchers interest focused on the identification of selective drugs, with the strong expectation to avoid adverse drug reactions (ADRs), very recently new research strategies resulted more appealing even as attempts to overcome the decline in productivity of the drug dis…

Methylation of cytokines gene promoters in IL-1β-treated human intestinal epithelial cells

Objective and design: Epigenetic regulation is important in the activation of inflammatory cells. In the present study, we evaluated if DNA-methylation variations are involved in Interleukin-1β (IL-1β)-induced intestinal epithelial cells activation. Materials and methods: Differentiated Caco-2 cells were exposed to IL-1β or to 5-azadeoxycytidine (5-azadC) for 24 or 48 h. Genome-wide methylation status was evaluated, while DNA methylation status at the promoter region of the gene encoding interleukin-6, 8 and 10 (IL-6, 8 and 10) was estimated. The levels of the corresponding gene products as well as DNA methyltransferases (DNMTs) quantity were assessed. Results: IL-1β decreased genomic m…

Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells

Antioxidant phytochemicals are investigated as novel treatments for supportive therapy in beta-thalassemia. The dietary indicaxanthin was assessed for its protective effects on human beta-thalassemic RBCs submitted in vitro to oxidative haemolysis by cumene hydroperoxide. Indicaxanthin at 1.0-10 microM enhanced the resistance to haemolysis dose-dependently. In addition, it prevented lipid and haemoglobin (Hb) oxidation, and retarded vitamin E and GSH depletion. After ex vivo spiking of blood from thalassemia patients with indicaxanthin, the phytochemical was recovered in the soluble cell compartment of the RBCs. A spectrophotometric study showed that indicaxanthin can reduce perferryl-Hb ge…

Anti-oxidant and anti-inflammatory properties of betalains from Cactus Pear

Anti-oxidant and anti-inflammatory properties of Betalains from Cactus Pear. C. Gentile1, A. Marconi1, M. A. Livrea2, G. Uzan1, P. D’Alessio1. 1 Inserm U602, Paris, France. 2 Dip. Farmacochimico, Tossicologico e Biologico, Università Palermo, Italy. Betalains of phytochemical origin, known as potent radical-scavengers in chemical and biological systems, have been tested in a model of inflammation. New phytochemicals are continuously inspected for potential pharmacological applications. The red betanin and the yellow indicaxanthin have recently been isolated and characterized from Cactus Pear. Reactive Oxygen Species may be toxic or display a regulatory character. During the inflammation rea…

Eryptosis by major components of a plasma-compatible mixture of oxysterols.

Pro-apoptotic activity of the phytochemical Indicaxanthin on colorectal carcinoma cells (Caco-2) and epigenetic CpG demethylation of the promoter and reactivation of the expression of p16

Phytochemicals play prominent roles in human diet and nutrition as protective redo-active substances in prevention of several disorders and chronic diseases in humans. Today, their function as potent modulators of the mammalian epigenome-regulated gene expression is rapidly emerging. In the present study antiproliferative effects of Indicaxanthin (Ind) from the fruits of Opuntia ficus-indica (1), and potential influence on DNA methylation has been investigated on Caco-2 cells, a human cell line of colorectal carcinoma. Ind caused a clear dose- and time-dependent decrease of the cell proliferation (IC(50) 50 M) associated to apoptosis as demonstrated by phosphatidylserine externalization an…

Expression of T-cadherin in tumor cells influences invasive potential of human hepatocellular carcinoma

Overexpression of T-cadherin (T-cad) transcripts occurs in approximately 50% of human hepatocellular carcinomas (HCCs). To elucidate T-cad functions in HCC, we examined T-cad protein expression in normal and tumoral human livers and hepatoma cell lines and investigated its influence on invasive potential of HCC using RNA interference silencing of T-cad expression in Mahlavu cells. Whereas T-cad expression was restricted to endothelial cells (EC) from large blood vessels in normal livers, it was up-regulated in sinusoidal EC from 8/15 invasive HCCs. Importantly, in three of them (38%) T-cad was detected in tumor cells within regions in which E-cadherin expression was absent. Among six hepato…

Antioxidant betalains from cactus pear (Opuntia ficus-indica) inhibit endothelial ICAM-1 expression.

It has been suggested that some pigments would have antioxidant properties and that their presence in dietary constituents would contribute to reduce the risk of oxidative stress–correlated diseases. Among others, inflammatory response depends on redox status and may implicate oxidative stress. Vascular endothelial cells are a direct target of oxidative stress in inflammation. We have tested the impact of the free radical scavenger and antioxidant properties of betalains from the prickle pear in an in vitro model of endothelial cells. Here we show the capacity of betalains to protect endothelium from cytokine- induced redox state alteration, through ICAM-1 inhibition. KEYWORDS: endothelial …

Changes in the Phytochemical Profile and Antioxidant Properties of Prunus persica Fruits after the Application of a Commercial Biostimulant Based on Seaweed and Yeast Extract

Plant biostimulants are formulations that are experiencing great success from the perspective of sustainable agriculture. In this work, we evaluated the effect derived from the application of a biostimulant based on algae and yeast extracts (Expando®) on the agronomic yield and nutraceutical profile of two different cultivars (“Sugar Time” and “West Rose”) of Prunus persica (peach). Although, at the agronomic level, significant effects on production yields were not recorded, the biostimulant was able to reduce the ripening time, increase the fruit size, and make the number of harvestable fruits homogeneous. From a nutraceutical point of view, our determinations v…

Phytochemical indicaxanthin suppresses 7-ketocholesterol-induced THP-1 cell apoptosis by preventing cytosolic Ca++ increase and oxidative stress

7-Ketocholesterol (7-KC)-induced apoptosis of macrophages is considered a key event in the development of human atheromas. In the present study, the effect of indicaxanthin (Ind), a bioactive pigment from cactus pear fruit, on 7-KC-induced apoptosis of human monocyte/macrophage THP-1 cells was investigated. A pathophysiological condition was simulated by using amounts of 7-KC that can be reached in human atheromatous plaque. Ind was assayed within a micromolar concentration range, consistent with its plasma level after dietary supplementation with cactus pear fruit. Pro-apoptotic effects of 7-KC were assessed by cell cycle arrest, exposure of phosphatidylserine at the plasma membrane, varia…

Pomological traits, sensory characteristics and antioxidant activity in fruits of nine loquat cultivars grown in Sicily.

Phytochemical Profile and Antioxidant, Antiproliferative, and Antimicrobial Properties of Rubus idaeus Seed Powder

In the context of the contemporary research on sustainable development and circular economy, the quest for effective strategies aimed at revaluation of waste and by-products generated in industrial and agricultural production becomes important. In this work, an ethanolic extract from red raspberry (Rubus idaeus) seed waste (WRSP) was evaluated for its phytochemical composition and functional properties in term of antioxidative, antiproliferative, and antimicrobial activities. Chemical composition of the extract was determined by both HPLC-ESI-MS/MS and spectrophotometric methods. Phytochemical analysis revealed that flavan-3-ols and flavonols were the major phenolic compounds contained in W…

Kinetics of the lipoperoxyl radical-scavenging of betanin and betanidin in solution.

The Application of a Plant Biostimulant Based on Seaweed and Yeast Extract Improved Tomato Fruit Development and Quality

Plant biostimulants are under investigation as innovative products to improve plant production and fruit quality, without resulting in environmental and food contaminations. Here, the effects of the application of Expando, a biostimulant based on seaweed and yeast extracts, on plant productivity, fruit ripening times, and fruit quality of Solanum lycopersicum var. Micro-Tom were evaluated. After biostimulant treatment, a two-week reduction of ripening times and a concomitant enhancement of the production percentage during the earliest ripening times, in terms of both fruit yield (+110%) and size (+85%), were observed. Concerning fruit quality, proximate analysis showed that tomatoes treated…

Omega-3 rich foods: Durum wheat spaghetti fortified with Portulaca oleracea

Abstract Portulaca oleracea is an annual succulent herb (purslane) with high antioxidant properties and high content of essential ω-3 and ω-6 fatty acids, ascorbic acid, α-tocopherol and β-carotene. In the present study, sensorial and chemical analyses of uncooked and cooked durum wheat pasta fortified with purslane from three different Sicilian areas and at three different concentrations (5, 10 and 15%) were estimated. The sensorial analysis showed that the scores of the overall acceptance decreased considerably in pasta with 15% purslane, while consumers appreciated pasta samples with 10% purslane. Chemical analysis highlighted that the addition of purslane gave pasta samples the potentia…

Vaccinium macrocarpon (Cranberry)-Based Dietary Supplements: Variation in Mass Uniformity, Proanthocyanidin Dosage and Anthocyanin Profile Demonstrates Quality Control Standard Needed

Vaccinium macrocarpon (syn. American Cranberry) is employed in dietary supplements (DS) with the aim to improve urinary tract well-being. This property is linked to the antiadhesion-activity of proanthocyanidins (PACs) against uropathogenic-bacteria. However, the current European legislation has been criticized for being weak and ineffective. Indeed, recent scientific works report mislabeled, contaminated, and adulterated supplements containing dangerous or unknown compounds, or sold at toxic doses. In this work, we analysed 24 DS that claim to contain cranberry, and to have a specific dosage of PACs. Our tests included the control of the good manufacturing practice according to the Europea…

Cytoprotective effects of indicaxanthin in beta-thalassemia red blood cells

Heterocyclic Scaffolds for the Treatment of Alzheimer's Disease

Background: The treatment and diagnosis of Alzheimer’s Disease (AD) are two of the most urgent goals for research around the world. The cognitive decline is generally associated with the elevated levels of extracellular senile plaques, intracellular neurofibril- lary tangles (NFTs), and with a progressive shutdown of the cholinergic basal forebrain neurons transmission. Even if several key targets are under fervent investigation in the cure of AD, till now, the only approved therapeutic strategy is the treatment of symptoms by using cholinesterases inhibitors. It has been demonstrated that both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes are not only responsible of…

Proanthocyanidins and Where to Find Them: A Meta-Analytic Approach to Investigate Their Chemistry, Biosynthesis, Distribution, and Effect on Human Health.

Proanthocyanidins (PACs) are a class of polyphenolic compounds that are attracting considerable interest in the nutraceutical field due to their potential health benefits. However, knowledge about the chemistry, biosynthesis, and distribution of PACs is limited. This review summarizes the main chemical characteristics and biosynthetic pathways and the main analytical methods aimed at their identification and quantification in raw plant matrices. Furthermore, meta-analytic approaches were used to identify the main plant sources in which PACs were contained and to investigate their potential effect on human health. In particular, a cluster analysis identified PACs in 35 different plant famili…

Betanin protects endothelial cell dysfunction produced by activated HL-60

Anti-inflamamtory effects of Sicilian pistachio (Pistacia vera L.) nut in an in vitro model of human intestinal epithelium

In silico, spectroscopic, and biological insights on annelated pyrrolo[3,2-e]pyrimidines with antiproliferative activity

The in silico COMPARE analysis was performed on 8-[3-(piperidino)propyl]-4,10-dimethyl-9-phenyl-6-(methylsulfanyl)-3,4-dihydropyrimido[1,2-c]pyrrolo[3,2-e]pyrimidin-2(8H)-one, a compound with promising antiproliferative activity, previously synthetized and screened against a panel of 60 human tumor cell lines. The results evidenced that this compound matches the biological properties of Chromomycin A3 and Actinomycin D, known drugs with high DNA binding affinity. Prompted by such results, a thorough spectroscopic investigation of its DNA aqueous solutions was performed, with the aim to verify its DNA-binding properties. DNA groove-binding interaction was assigned by UV-vis spectrophotometri…

Yield, pomological characteristics, bioactive compounds and antioxidant activity of <i>Annona cherimola Mill.</i> grown in mediterranean climate

The agronomic and qualitative responses of the cherimoya (Annona cherimola Mill.) fruit grown in Mediterranean climate are not properly studied. Fruits of Fino de Jete, the most diffused worldwide cultivar of cherimoya, and Torre 1 a new genotype obtained by breeding program in Sicily, Italy, were collected at commercial ripening and subjected to productive (yield efficiency, number of fruits, crop load), analytical (fruit weight, transversal diameter, longitudinal diameter, total soluble solid content, titratable acidity, seed weight, seed number, peel and pulp weight, pulp/seed ratio and colorimetric analysis), bioactive compound content (total antioxidant activity, Phenolic and Carotenoi…

Double chained naphthalenes as G4 binders

Oxysterol mixture in hypercholesterolemia-relevant proportion causes oxidative stress-dependent eryptosis.

Background/Aims: Oxysterol activity on the erythrocyte (RBC) programmed cell death (eryptosis) had not been studied yet. Effects of an oxysterol mixture in hyper-cholesterolemic-relevant proportion, and of individual compounds, were investigated on RBCs from healthy humans. Methods: Membrane phosphatidylserine (PS) externalization, calcium entry, ROS production, amino-phospholipid translocase (APLT) activity were evaluated by cytofluorimetric assays, cell volume from forward scatter. Prostaglandin PGE2 was measured by ELISA; GSH-adducts and lipoperoxides by spectrophotometry. Involvement of protein kinase C and caspase was investigated by inhibitors staurosporin, calphostin C, and Z-DEVD-FM…

Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix.

Purpose: This study investigated the absorption mechanism of the phytochemicals indicaxanthin and betanin and the influence of their food matrix (cactus pear and red beet) on the intestinal transport. Methods: Trans-epithelial transport of dietary-consistent amounts of indicaxanthin and betanin in Caco-2 cell monolayers seeded on TranswellR inserts was measured in apical to basolateral (AP-BL) and basolateral to apical (BL-AP) direction, under an inwardly directed pH gradient (pH 6.0/7.4, AP/BL) mimicking luminal and serosal sides of human intestinal epithelium. The effect of inhibitors of membrane transporters on the absorption was also evaluated. Contribution of the paracellular route was…

Effect of opuntia ficus-indica mucilage edible coating on quality, nutraceutical, and sensorial parameters of minimally processed cactus pear fruits

Cactus pear (Opuntia ficus-indica (L.) Mill.) is a non-climacteric fruit with a relatively short postharvest life span, being very sensitive to water loss, darkening and decay. Cactus pear is a spiny fruit, and the presence of glochids limits fruit consumption and diffusion

Phytochemical Indicaxanthin Inhibits Colon Cancer Cell Growth and Affects the DNA Methylation Status by Influencing Epigenetically Modifying Enzyme Expression and Activity

<b><i>Background:</i></b> Recently, we have shown anti-proliferative and pro-apoptotic effects of indicaxanthin associated with epigenetic modulation of the onco-suppressor <i>p16</i><sup><i>INK4a</i></sup> in the human colon cancer cell line CACO2. In the present study, the epigenetic activity of indicaxanthin and the mechanisms involved were further investigated in other colorectal cancer cell lines. <b><i>Methods:</i></b> LOVO1, CACO2, HT29, HCT116, and DLD1 cells were used to evaluate the potential influence of consistent dietary concentrations of indicaxanthin on DNA methylation, and the epigenetic mech…

Increased resistance to oxidation of betalain-enriched human low density lipoproteins

Betalains are natural pigments recently considered as compounds with potential antioxidative properties. In this work, ex vivo plasma spiking of pure either betanin or indicaxanthin, followed by isolation of low density lipoprotein (LDL), and measurement of its resistance to copper-induced oxidation, has been used to research if these betalains can bind to LDL and prevent oxidation of LDL lipids. When pooled human plasma from 10 healthy volunteers was incubated in the presence of 25-100 microM either betanin or indicaxanthin, incorporation of both compounds in LDL was observed, with a maximum binding of 0.52 +/- 0.08, and 0.51 +/- 0.06 nmoles of indicaxanthin and betanin, respectively, per …

Anthocyanins: Biosynthesis, Distribution, Ecological Role, and Use of Biostimulants to Increase Their Content in Plant Foods—A Review

In the past century, plant biostimulants have been increasingly used in agriculture as innovative and sustainable practice. Plant biostimulants have been mainly investigated as potential agents able to mitigate abiotic stress. However, few information is available about their ability to influence fruit quality or change fruit phytochemical composition. In particular, very little is known about their effects on anthocyanin synthesis and accumulation. Due to the increasing demand of consumers for healthier foods with high nutraceutical values, this review tries to fill the gap between anthocyanin content and biostimulant application. Here, we elucidate the chemical structure, biosynthetic pat…

Chemical partitioning and DNA fingerprinting of some pistachio (Pistacia vera L.) varieties of different geographical origin

The genus Pistacia (Anacardiaceae family) is represented by several species, of which only P. vera L. produces edible seeds (pistachio). Despite the different flavor and taste, a correct identification of pistachio varieties based on the sole phenotypic character is sometimes hard to achieve. Here we used a combination of chemical partitioning and molecular fingerprinting for the unequivocal identification of commercial pistachio seed varieties (Bronte, Kern, Kerman, Larnaka, Mateur and Mawardi) of different geographical origin. The total phenolic content was higher in the variety Bronte followed by Larnaka and Mawardi cultivars. The total anthocyanin content was higher in Bronte and Larnak…

Methylation decrease of BECN1 gene induced by phytochemical Indicaxantin in Caco2 cells: an epigenetic hypothesis of autophagy

Autophagy is a highly conserved catabolic process that degrades and recycles intracellular components through the lysosomes [1]. The role of this process in tumorigenesis and tumor progression is controversial: in the early stages, it can block tumor growth and conversely it can promote its progression in the later stages [2]. The tumor suppressor BECN1 gene, encodes the protein Beclin 1, a marker of autophagy down-regulated in several types of cancer, such as colorectal cancer [3]. There are a lot of both genetic and environmental risk factors for colorectal cancer, including diet: for this reason, in accordance with epidemiological studies, consumption of foods rich in phytochemicals is w…

New benzothieno[3,2-d]-1,2,3-triazines with antiproliferative activity: synthesis, spectroscopic studies, and biological activity.

New benzothieno[3,2-d]-1,2,3-triazines, together with precursors triazenylbenzo[b]thiophenes, were designed, synthesized and screened as anticancer agents. The structural features of these compounds prompted us to investigate their DNA binding capability through UV–vis absorption titrations, circular dichroism, and viscometry, pointing out the occurrence of groove-binding. The derivative 3-(4-methoxy-phenyl)benzothieno[3,2-d]-1,2,3-triazin-4(3H)-one showed the highest antiproliferative effect against HeLa cells and was also tested in cell cycle perturbation experiments. The obtained results assessed for the first time the anticancer activity of benzothieno[3,2-d]-1,2,3-triazine nucleus, and…

Phytochemical indicaxanthin prevents 7-ketocholesterol-induced oxidative stress and cell cycle arrest in murine macrophages

Antiinflammatory effects of pistachio nut proanthocyanidins in LPS-stimulated RAW264.7 cells

Design, synthesis, and biological evaluation of a new class of benzo[b]furan derivatives as antiproliferative agents, with in silico predicted antitubulin activity

A new series of 3-benzoylamino-5-(1H-imidazol-4-yl)methylaminobenzo[b]furans were synthesized and screened as antitumor agents. As a general trend, tested compounds showed concentration-dependent antiproliferative activity against HeLa and MCF-7 cancer cell lines, exhibiting GI50 values in the low micromolar range. In most cases, insertion of a methyl substituent on the imidazole moiety improved the antiproliferative activity. Therefore, methyl-imidazolyl-benzo[b]furans compounds were tested in cell cycle perturbation experiments, producing cell cycle arrest with proapoptotic effects. Their core similarity to known colchicine binding site binders led us to further study the structure featur…

Anti-inflammatory properties of betanin from cactus pear (Opuntia Ficus Indica) in an endothelial cell model.

SELECTIVE G-QUADRUPLEX STABILIZERS: SALPHEN-LIKE COMPLEXES WITH ANTIPROLIFERATIVE ACTIVITY

Schiff base complexes derived from N,N!-bridged tetradentate ligands involving N2O2 donor atoms present very favourable features to act as G4 binders. Thus, a series of square-planar and square pyramidal metal complexes, ML2+ (M = Ni, Cu, and Zn), have been synthesized and characterized.

IL-1β maintains the DNA hypermethylation of anti-inflammatory IL-10 gene in a human intestinal epithelial cell line

Intestinal inflammation is a natural process crucial to maintain gut integrity, but its deregulation is involved in the pathogenesis of severe intestinal disorders[1]. Intestinal epithelial cells play a crucial role in the inflammatory response, modulating the immune cell exposure to antigens and by their ability to secrete many inflammatory mediators. IL-1β represents a pivotal player: secreted by infiltrated leucocytes, it induces the expression of several pro-inflammatory genes. Also the anti-inflammatory IL-10, whose function is to terminate the inflammatory process, modulates the intestinal physiology[2]. Recent clinical reports showed that patients with ulcerative colitis in remission…

Non-flavonoid polyphenols in osteoporosis: preclinical evidence

The development of progressive osteopenia and osteoporosis (OP) is due to the imbalance between bone resorption and bone formation, determining a lower bone resistance, major risks of fractures, with consequent pain and functional limitations. Flavonoids, a class of polyphenols, have been extensively studied for their therapeutic activities against bone resorption, but less attention has been given to a whole series of molecules belonging to the polyphenolic compounds. However, these classes have begun to be studied for the treatment of OP. In this systematic review, comprehensive information is provided on non-flavonoid polyphenolic compounds, and we highlight pathways implicated in the ac…

POMOLOGICAL TRAITS, SENSORY CHARACTERISTICS, AND ANTIOXIDANT ACTIVITY IN FRUITS OF NINE LOQUAT CULTIVARS GROWN IN SICILY

Loquat cultivation in Italy currently aims at offering a wider choice of cultivars to growers. The present study determined commercial quality, characterized the antioxidant capacity, and quantified the major bioactive compounds of some local ('BRT 20', 'Claudia', 'Nespolone di Trabia', 'Sanfilippara') and international ('Algerie', 'El Buenet', 'Bueno', 'Golden Nugget' and 'Peluche') cultivars. Fruit was harvested at commercial ripening and chemical-physical determinations of weight, diameters, skin and flesh color, soluble solid content, tritable acidity, antioxidant activity and polyphenol content, and sensory analyses were carried out. Data showed a large variability among genotypes and …

Effect of addition of Opuntia ficus-indica mucilage on the biological leavening, physical, nutritional, antioxidant and sensory aspects of bread

The addition of active compounds to enhance the functional properties of foods is a quite common practice. Recently, bread became one of the target foods to incorporate functional ingredients such as those deriving from Opuntia spp. So far, only Opuntia ficus-indica cladodes in powder has been tested. The addition of fresh O. ficus-indica mucilage (in substitution to water) did not influence the biological leavening of the doughs. The resulting breads showed a biological role of the cactus mucilage, because their antioxidant activity was higher than that of control wheat bread. The sensory analysis indicated a general appreciation of the breads enriched with O. ficus-indica mucilage by the …

Kinase Inhibitors in Multitargeted Cancer Therapy

The old-fashioned anticancer approaches, aiming in arresting cancer cell proliferation interfering with non-specific targets (e.g. DNA), have been replaced, in the last decades, by more specific target oriented ones. Nonetheless, single-target approaches have not always led to optimal outcomes because, for its complexity, cancer needs to be tackled at various levels by modulation of several targets. Although at present, combinations of individual single-target drugs represent the most clinically practiced therapeutic approaches, the modulation of multiple proteins by a single drug, in accordance with the polypharmacological strategy, has become more and more appealing. In the perspective of…

Betacyanins as phenol antioxidants. Chemistry and mechanistic aspects of the lipoperoxyl radical-scavenging activity in solution and liposomes.

Reaction kinetics of betanin and its aglycone betanidin towards peroxyl radicals generated from the azo-initiated oxidation of methyl linoleate in methanol, and of a heterogeneous aqueous/soybean phosphatidylcholine liposomal system, were studied by monitoring formation of linoleic acid hydroperoxides and consumption of the pigments. Betanin was a weak retarder in methanol, and an effective chain breaking antioxidant in the liposomal model, indicating that kinetic solvent effects and partition in lipid bilayers may affect its activity. Betanidin behaved as a chain terminating antioxidant in both models. Kinetic parameters characterizing peroxyl radical-scavenging activity showed that betani…

Science and Healthy Meals in the World: Nutritional Epigenomics and Nutrigenetics of the Mediterranean Diet

The Mediterranean Diet (MD), UNESCO Intangible Cultural Heritage of Humanity, has become a scientific topic of high interest due to its health benefits. The aim of this review is to pick up selected studies that report nutrigenomic or nutrigenetic data and recapitulate some of the biochemical/genomic/genetic aspects involved in the positive health effects of the MD. These include (i) the antioxidative potential of its constituents with protective effects against several diseases; (ii) the epigenetic and epigenomic effects exerted by food components, such as Indacaxanthin, Sulforaphane, and 3-Hydroxytyrosol among others, and their involvement in the modulation of miRNA expression; (iii) the …

A NEW DOPAMINE-AMINOACID CONJUGATE: SYNTHESIS AND DETERMINATION OF PHYSICO-CHEMICAL PROPERTIES USEFUL TO CROSS THE BBB

Synthesis, antiproliferative activity, and in silico insights of new 3-benzoylamino-benzo[ b ]thiophene derivatives

A new series of 3-benzoylamino-5-imidazol-5-yl-benzo[b]thiophenes and the parent amino derivatives were synthesized and screened as antitumor agents. All tested compounds showed concentration-dependent antiproliferative activity profile against HeLa cell line, exhibiting GI50 values in the low micromolar range. The most active compounds were tested in cell cycle perturbation experiments. A rapid accumulation of cells in the G2/M phase, with a concomitant reduction of cells in both the S and G0/G1 phases, was observed, suggesting that cell exposure to selected derivatives produces mitotic failure. To rationalize the biological results, the 3-benzoylamino-benzo[b]thiophenes were analyzed thro…

Synthesis and biological activities of a new class of heat shock protein 90 inhibitors, designed by energy-based pharmacophore virtual screening

The design through energy-based pharmacophore virtual screening has led to aminocyanopyridine derivatives as efficacious new inhibitors of Hsp90. The synthesized compounds showed a good affinity for the Hsp90 ATP binding site in the competitive binding assay. Moreover, they showed an excellent antiproliferative activity against a large number of human tumor cell lines. Further biological studies on the derivative with the higher EC50 confirmed its specific influence on the cellular pathways involving Hsp90.

In Silico Insights into the SARS CoV-2 Main Protease Suggest NADH Endogenous Defences in the Control of the Pandemic Coronavirus Infection

COVID-19 is a pandemic health emergency faced by the entire world. The clinical treatment of the severe acute respiratory syndrome (SARS) CoV-2 is currently based on the experimental administration of HIV antiviral drugs, such as lopinavir, ritonavir, and remdesivir (a nucleotide analogue used for Ebola infection). This work proposes a repurposing process using a database containing approximately 8000 known drugs in synergy structure- and ligand-based studies by means of the molecular docking and descriptor-based protocol. The proposed in silico findings identified new potential SARS CoV-2 main protease (MPRO) inhibitors that fit in the catalytic binding site of SARS CoV-2 MPRO. Several sel…

Preliminary Investigation of Biogenic Amines in Type I Sourdoughs Produced at Home and Bakery Level

During a survey for isolating sourdough lactic acid bacteria (LAB), 20 dough samples produced at the bakery level (BL) or home-made (HM) were collected. An enzyme-based colorimetric method revealed a total biogenic amines (BAs) concentration in the range 41.4–251.8 ppm for six (three BL and three HM) sourdoughs characterised by unpleasant odours. Eight BAs generally investigated in foods were identified and quantified from these six samples by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS). Only one HM sample contained almost all analysed BAs. Tryptamine was exclusively detected in HM sourdoughs (0.71–24.1 ppm). Putrescine, tryptamine, …

Bioactive effects of citrus flavonoids and role in the prevention of atherosclerosis and cancer

Citrus fruits are the main fruits of the Mediterranean diet and have been long recognized for their beneficial effects on human health. Observational studies have shown a significant association between dietary flavonoid intake and reduced risk of cardiovascular and malignant diseases. The beneficial effects of citrus fruits on human health appear to be due to their high content in vitamins, minerals and fibers. In particular, the antioxidant and anti-inflammatory activities have been indicated as some of the mechanisms through which citrus fruits may thwart the development of chronic degenerative diseases such as atherosclerosis and cancer. This review would critically examine the results …

Quality changes in fresh-cut mango cubes submitted to different gas partial pressure of active MAPs

The study was performed to assess chemical-physical and sensory quality changes in 4±1°C stored fresh-cut mangos and to test the effect of active modified atmosphere packaging (MAP) with different gas partial pressures. Sicilian fruits of ‘Keitt’ mango (Mangifera indica L.) were immerged in hydrogen peroxide (H2O2) after being peeled. Next, the flesh was cut in cubes and dipped in citric acid (0.5%, w/v) and ascorbic acid (0.5%, w/v). Treated fruits were placed in a non-perforated high density polyethylene package flushing different gas mixtures and kept at 4°C for 21 days. We used four different gas partial pressures: a) 60 kPa N2, 30 kPa CO2 and 10 kPa O2; b) 30 kPa CO2 and 70 kPa N2; c) …

Bioactive triterpenes of protium heptaphyllum gum resin extract display cholesterol-lowering potential

Hypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach, but they may be insufficient due to the onset of resistance mechanisms and side effects. Consequently, patients with mild hypercholesterolemia prefer the use of food supplements since these are perceived to be safer. Here, we investigate the phytochemical profile and cholesterol-lowering potential of Protium heptaphyllum gum resin extract (PHE). Chemical characterization via HPLC-APCI-HRMS2 and…

Salphen metal complexes as potential anticancer agents: interaction profile and selectivity studies toward the three G-quadruplex units in the KIT promoter

DNA G-rich sequences can organize in four-stranded structures called G-quadruplexes (G4s). These motifs are enriched in significant sites within the human genomes, including telomeres and promoters of cancer related genes. For instance, KIT proto-oncogene promoter, associated with diverse cancers, contains three adjacent G4 units, namely Kit2, SP, and Kitt. Aiming at finding new and selective G-quadruplex binders, we have synthesized and characterized five non-charged metal complexes of Pt(II), Pd(II), Ni(II), Cu(II) and Zn(II) of a chlorine substituted Salphen ligand. The crystal structure of the Pt(II) and Pd(II) complexes was determined by XRPD. FRET measurements indicated that Pt(II) an…

Flavonoids in Bone Erosive Diseases: Perspectives in Osteoporosis Treatment

Imbalance of bone homeostasis, with excessive bone resorption compared with bone formation, leads to the development of progressive osteopenia leading to lower bone resistance to load, with consequent pain and functional limitations. Phytochemicals with therapeutic and preventive effects against bone resorption have recently received increasing attention since they are potentially more suitable for long-term use than traditional therapeutic chemical compounds. In this systematic review of the literature of the past 5 years, comprehensive information is provided on flavonoids with potential antiresorption and pro-osteogenic effects. It aims to highlight the molecular mechanisms of these mole…

Antiproliferative properties and g-quadruplex-binding of symmetrical naphtho[1,2-b:8,7-b’]dithiophene derivatives

Background: G-quadruplex (G4) forming sequences are recurrent in telomeres and promoter regions of several protooncogenes. In normal cells, the transient arrangements of DNA in G-tetrads may regulate replication, transcription, and translation processes. Tumors are characterized by uncontrolled cell growth and tissue invasiveness and some of them are possibly mediated by gene expression involving G-quadruplexes. The stabilization of G-quadruplex sequences with small molecules is considered a promising strategy in anticancer targeted therapy. Methods: Molecular virtual screening allowed us identifying novel symmetric bifunctionalized naphtho[1,2-b:8,7-b’]dithiophene ligands as interesting ca…

Pomological Traits, Sensory Profile and Nutraceutical Properties of Nine Cultivars of Loquat (Eriobotrya japonica Lindl.) Fruits Grown in Mediterranean Area

In this paper the diversity of fruit quality within nine loquat cultivars, including five international affirmed cultivars (Algerie, Golden Nugget, Peluche, Bueno, El Buenet) and four local cultivars (Sanfilippara, Nespolone di Trabia, BRT20 and Claudia), were investigated in order to discriminate the variation in pomological characteristics, sensory profile, and antioxidant properties. Finally, to evaluate potential bioactivity, antiproliferative activity of hydrophilic extracts from loquat fruits was assessed, at dietary relevant concentrations, against three human epithelial cell lines. Even though the international cultivars confirmed an appropriate level of commercial qualities in asso…

PROGETTAZIONE, SINTESI E VALUTAZIONE BIOLOGICA DI NUOVI INIBITORI DI HSP90

Physicochemical, Nutraceutical and Sensory Traits of Six Papaya (Carica papaya L.) Cultivars Grown in Greenhouse Conditions in the Mediterranean Climate

Six papaya (Carica papaya L.) cultivars, grown in a Mediterranean climate under greenhouse conditions, were screened for physicochemical properties, antioxidant capacity, nutritional and sensory characteristics. The fruits, harvested with more than 50% of yellow surface (between 60% and 77%) were tested for carotenoids content, phenolic content, reducing activity (ABTS) and cellular antioxidant activity (CAA50). The physicochemical traits were measured in terms of the titratable acidity and soluble content whereas proximal composition along with moisture, fats, total sugar, ash, vitamin A, C and E content. Moreover, the sensory profile was analyzed by a semi-trained panel. Although the six …

Selective G-quadruplex stabilizers: Schiff-base metal complexes with anticancer activity

The affinity of three square-planar nickel(II) (1), copper(II) (2) and zinc(II) (3) Schiff-base complexes for wild-type human telomeric (h-Telo) and protooncogene c-myc G-quadruplex (G4) DNA was investigated by UV-visible absorption spectroscopy and circular dichroism. DNA-binding constants (Kb) were determined by spectrophotometric titrations for both G4-DNA and B-DNA. The results obtained point out that the three metal complexes selectively bind G4-DNA with higher affinity, up to two orders of magnitude, with respect to B-DNA. The nickel(II) complex 1 was found to be the most effective G4-DNA stabilizer and the Kb values decrease in the order 1 > 2 ≈ 3. Innovative computational investigat…

Polymeric proanthocyanidins from Sicilian pistachio (Pistacia vera L.) nut extract inhibit lipopolysaccharide-induced inflammatory response in RAW 264.7 cells

Positive effects of pistachio nut consumption on plasma inflammatory biomarkers have been described; however, little is known about molecular events associated with these effects. We studied the anti-inflammatory activity of a hydrophilic extract from Sicilian Pistacia L. (HPE) in a macrophage model and investigated bioactive components relevant to the observed effects. HPE oligomer/polymer proanthocyanidin fractions were isolated by adsorbance chromatography, and components quantified as anthocyanidins after acidic hydrolysis. Isoflavones were measured by gradient elution HPLC analysis. RAW 264.7 murine macrophages were pre-incubated with either HPE (1- to 20-mg fresh nut equivalents) or i…

Phytochemical indicaxanthin suppresses 7-ketocholesterol-induced THP-1 cell apoptosis by preventing cytosolic Ca(2+) increase and oxidative stress.

7-Ketocholesterol (7-KC)-induced apoptosis of macrophages is considered a key event in the development of human atheromas. In the present study, the effect of indicaxanthin (Ind), a bioactive pigment from cactus pear fruit, on 7-KC-induced apoptosis of human monocyte/macrophage THP-1 cells was investigated. A pathophysiological condition was simulated by using amounts of 7-KC that can be reached in human atheromatous plaque. Ind was assayed within a micromolar concentration range, consistent with its plasma level after dietary supplementation with cactus pear fruit. Pro-apoptotic effects of 7-KC were assessed by cell cycle arrest, exposure of phosphatidylserine at the plasma membrane, varia…

Sicilian pistachio (Pistacia vera L.) nut inhibits expression and release of inflammatory mediators and reverts the increase of paracellular permeability in IL-1b-exposed human intestinal epithelial cells

Background Dietary approaches to control inflammatory bowel diseases (IBD) may include proanthocyanidin-rich foods. Our previous research showed that a hydrophilic extract from Sicilian pistachio nut (HPE) contains sub- stantial amounts of proanthocyanidins and possesses anti- inflammatory activities. Purpose We studied the effects of HPE and of its poly- meric proanthocyanidin fraction (PPF) in a cell model that simulated some conditions of IBD, consisting of interleukin (IL)-1b-stimulated Caco-2 cells. Methods HPE was prepared by Pistacia vera L. nuts, and PPF was isolated from HPE by adsorbance chromatogra- phy. Proanthocyanidins were quantified as anthocyanidins after acidic hydrolysis.…

Bioactive components of caper (Capperis spinosa L.) from Sicily and antioxidant effects in a red meat simulated gastric digestion

An increasing body of evidence on the association between adherence to the Mediterranean diet and healthy status is being accumulated. Floral buds of Capparis spinosa L. are commonly used in the Mediterranean cuisine as flavoring for meat and other foods. The present study evaluated bioactive components and antioxidant activity of Sicilian capers stabilized in salt. Whereas alpha-tocopherol was absent, low levels of gamma-tocopherol and vitamin C were measured. With reference to one serving size (8.6 g of capers), rutin was 13.76 mg, isothiocyanates, recently acknowledged as anticarcinogen phytochemicals, were 42.14 micromol, total phenols were 4.19 mg of gallic acid equivalents (GAE), and …

Presence of endothelial progenitor cells, distinct from mature endothelial cells, within human CD146+ blood cells.

SummaryCD146 is an adhesion molecule present on endothelial cells throughout the vascular tree. CD146 is also expressed by circulating endothelial cells (CECs) widely considered to be mature endothelial cells detached from injured vessels. The discovery of circulating endothelial progenitor cells (EPCs) originating from bone marrow prompted us to investigate whether CD146 circulating cells could also contains EPCs. We tested this hypothesis using an approach combining elimination of CECs by an adhesion step, followed by immunomagnetic sorting of remaining CD146+ cells from the non adherent fraction of cord blood mononuclear cells. When cultured under endothelial-promoting conditions, these …

Betanin inhibits icam-1 expression in endothelial cells co-cultured with activated HL-60 cells

Mucilage-Based and Calcium Ascorbate Edible Coatings Improve Postharvest Quality and Storability of Minimally Processed Cactus Pear Fruit Stored under Passive Atmosphere

The minimally processed fruit and vegetable industry showed rapid growth worldwide, primarily due to the increasing consumer need for ready-to-eat fresh products characterized by high nutritional, sensory and healthy value. The postharvest life of peeled cactus pear fruits is relatively short, due to the processing operations that affect fruit integrity and cause metabolic disfunctions, as well as pulp browning, microbial growth, loss of firmness, off-flavor development, and nutraceutical value loss. In this study, we investigated the effects of mucilage-based (OFI) and calcium ascorbate edible coating on minimally processed cactus pear summer-ripening fruit, cold stored under passive atmos…

Sicilian pistachio nut extract inhibits inflammatory response in lipopolysaccharide-stimulated macrophages.

Transepithelial transport of betalainic phytochemicals in Caco-2 cell monolayers.

Phytochemical profile and antioxidant properties of the edible and non-edible portions of black sapote (Diospyros digyna Jacq.)

This study evaluated the phytochemical profile and antioxidative properties of the edible and non-edible portions of black sapote. The phytochemical analysis highlighted the presence of several bioactive compounds, differently distributed among peel, pulp and seeds. In particular, the peel resulted rich of flavan-3-ols and proanthocyanidins, whereas seeds contained high amount of organic acids, including ferulic, citric and sinapic acids. Concerning functional properties, both edible and non-edible portions showed a significant prevention of lipid peroxidation in a cell-based model. Moreover, the results suggested that the antioxidant protection involved both redox active properties and gen…

Pasta fortificata ad azione antiossidante. Uso della Portulaca Oleracea

Un alimento può essere considerato “funzionale” quando ne è dimostra- ta la sua influenza benefica su uno o più funzioni del corpo.

Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16(INK4a) gene in human colorectal carcinoma (Caco-2) cells.

Phytochemicals may exert chemo-preventive effects on cells of the gastro-intestinal tract by modulating epigenome-regulated gene expression. The effect of the aqueous extract from the edible fruit of Opuntia ficus-indica (OFI extract), and of its betalain pigment indicaxanthin (Ind), on proliferation of human colon cancer Caco-2 cells has been investigated. Whole extract and Ind caused a dose-dependent apoptosis of proliferating cells at nutritionally relevant amounts, with IC50 400 ± 25 mg fresh pulp equivalents/mL, and 115 ± 15 μM (n = 9), respectively, without toxicity for post-confluent differentiated cells. Ind accounted for ∼80% of the effect of the whole extract. Ind did not cause ox…

Antioxidant activity and phenolic composition in pomegranate (Punica granatumL.) genotypes from south Italy by UHPLC-Orbitrap-MS approach

Background: Pomegranate fruits are a rich source of polyphenols with numerous health-promoting effects. Pomegranate juices of five genotypes ('Mollar', 'Kingdom', 'Dente di Cavallo', and two old populations 'Francofonte' and 'Santa Tecla') were evaluated regarding anthocyanin and non-anthocyanin phenolic contents using ultrahigh performance liquid chromatography (UHPLC)-Orbitrap-mass spectrometry (MS). Moreover, total antioxidant activity (TAA) was evaluated using a 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assay.; Results: Twenty-three phenolic compounds were identified. Cyanidin-3,5-O-diglucoside and pelargonidin-3,5-O-diglucoside were the most represent…

In vitro digestion of betalainic foods. Stability and bioaccessibility of betaxanthins and betacyanins and antioxidative potential of food digesta.

Betalains are considered to be bioactive dietary phytochemicals. The stability of betacyanins and betaxanthins from either fresh foods or manufactured products of cactus pear fruit ( Opuntia ficus indica L. Mill. cv. Gialla and Rossa) and red beet ( Beta vulgaris L. ssp. vulgaris) was assessed in a simulated oral, gastric, and small intestinal digestion and compared with the digestive stability of purified pigments. A minor loss of indicaxanthin, at the gastric-like environment only, and a decrease of vulgaxanthin I through all digestion steps were observed, which was not affected by food matrix. In contrast, food matrix prevented decay of betanin and isobetanin at the gastric-like environm…

Protective effects of melatonin in inflamed intestinal epithelium are associated with reduced NF-κB activation and changes in DNA methylation status

Melatonin is the main product of the pineal gland but is also released in the gastrointestinal tract (GIT). Production of melatonin at GIT is independent of the photoperiod and contributes almost completely to plasma melatonin concentration during daylight hours. The physiological role of melatonin at GIT is poorly characterized but recently anti-inflammatory effects have been reported. In this study, we evaluated the effect of Melatonin in intestinal epithelial cells (IEC) stimulated by Interleukin-1β. Our results clearly show that melatonin at micromolar concentrations inhibits the inflammatory response in IEC. The protective effect is expressed through a marked decrease in release and ex…

Terpenoid treatment in osteoporosis: this is where we have come in research.

Lower bone resistance to load is due to the imbalance of bone homeostasis, where excessive bone resorption, compared with bone formation, determines a progressive osteopenia, leading to a high risk of fractures and consequent pain and functional limitations. Terpenoids, with their activities against bone resorption, have recently received increased attention from researchers. They are potentially more suitable for long-term use compared with traditional therapeutics. In this review of the literature of the past 5 years, we provide comprehensive information on terpenoids, with their anti-osteoporotic effects, highlighting molecular mechanisms that are often in epigenetic key and a possible p…

NiII, and ZnII Schiff Base Complexes: Telomeric G-quadruplex Stabilizers

Recently, NiII and ZnII metal complexes of the ligand Salpyrim have been synthesized and characterized. Their affinity for wild-type h-Telo G-quadruplex DNA and for calf thymus DNA was investigated by UV absorption spectroscopy, circular dichroism and viscometry. The data collectively suggest that both complexes bind effectively to G-quadruplexes by direct end-stacking, stabilizing the oligonucleotide secondary structure. The two complexes are also typical B-DNA intercalators. Remarkably, their binding constants, Kb, with the G4s structures are about 10 fold higher than those with B-DNA, highlighting the selectivity. Experiments to evaluate the biological activity of the two complexes again…

Pomological, Sensorial, Nutritional and Nutraceutical Profile of Seven Cultivars of Cherimoya (Annona cherimola Mill)

In this work, the food quality of four international (Campas, Chaffey, Fino de Jete and White) and three local (Daniela, Torre1 and Torre2) cultivars of Cherimoya (Annona cherimola Mill) was investigated. With this aim, pomological traits, sensorial attributes, physiochemical parameters (pH, total soluble content and total acidity), nutritional composition (macro- and micro-nutrients) and nutraceutical values (bioactive compounds, radical scavenging and antioxidant properties) were evaluated. Among the seven observed cultivars, Fino de Jete was identified as the best, not only for its commercial attributes such as pomological traits and physiochemical values, but also for its nutritional co…

IL-1. induces DNA demethylation at genome level and in specific CpG sites of IL-6 and IL-8 genes in human intestinal epithelial cells

Inflammation is a complex physiological response that requires the activity of a sophisticated regulatory network involving the activation of specific genes for defense, tissue repair and remodeling. Although transcriptional activation has been shown to be critical in the regulation of inflammatory genes (1) the role of epigenetic phenomena in the modulation of the inflammatory response is now emerging (2). Specifically, it has been recently reported that proinflammatory stimuli induce DNA demethylation in the interleukin IL-1 promoter of human articular chondrocytes (3). IL-1 cytokine, among several proinflammatory agents, represents an essential player in the inflammatory conditions of …

Chemical Profile and Biological Activity of Cherimoya (Annona cherimola Mill.) and Atemoya (Annona atemoya) Leaves

Annona cherimola (Cherimoya) and Annona atemoya (Atemoya) are tropical plants known for their edible fruit. Scientific data suggest that their leaves, used in traditional medicine in the form of teas or infusions without evidence of toxicity, contain several bioactive compounds. However, only Annona muricata among all the Annona species is currently used in the nutraceutical field, and its dried leaves are marketed for tea preparation. In this work, we explored the nutraceutical potential of Atemoya and Cherimoya leaves, by evaluating their chemical profile and functional properties. Phytochemical analyses showed large amounts of phenolic compounds, in particular proanthocyanidins, and iden…

Food quality and nutraceutical value of nine cultivars of mango (Mangifera indica L.) fruits grown in Mediterranean subtropical environment

Mango (Mangifera indica L.) quality is strongly influenced by genotype but individuating the most appropriate harvesting time is essential to obtain high quality fruits. In this trial we studied the influences of the ripening stage at harvest (mature-ripe or green-ripe) on quality of ready to eat mango fruits from nine cultivars (Carrie, Keitt, Glenn, Manzanillo, Maya, Rosa, Osteen, Tommy Atkins and Kensington Pride) grown in the Mediterranean subtropical climate through physicochemical, nutraceutical, and sensory analysis. Our results show a large variability among the different observed genotypes and in dependence of the ripening stage at harvest. With the exception of Rosa, mature-ripe f…

Antioxidant Activity of Sicilian Pistachio (Pistacia veraL. Var. Bronte) Nut Extract and Its Bioactive Components

Pistacia vera L. is the only species of Pistacia genus producing edible nuts. This paper investigates the antioxidant potential of a Sicilian variety of pistachio nut by chemical as well as biological assays and measured antioxidant vitamins and a number of antioxidant polyphenols in either the hydrophilic and/or the lipophilic nut extract. In accordance with the majority of foods, the total antioxidant activity, measured as a TAA test, was much higher (50-fold) in the hydrophilic than in the lipophilic extract. Substantial amounts of total phenols were measured. The hydrophilic extract inhibited dose-dependently both the metal-dependent and -independent lipid oxidation of bovine liver micr…

Food Quality, Sensory Attributes and Nutraceutical Value of Fresh “Osteen” Mango Fruit Grown under Mediterranean Subtropical Climate Compared to Imported Fruit

Mango is a fruit with a very short shelf-life due to its rapid ripeness after harvest

Studies on a new potential dopaminergic agent: in vitro BBB permeability, in vivo behavioural effects and molecular docking evaluation.

2-Amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-PHEN) has been previously synthesized to obtain a potential prodrug capable of release dopamine (DA) into CNS. However, DA-PHEN could act per se as a dopaminergic drug. In this study, the permeability transport (Pe), obtained by parallel artificial permeability assay (PAMPA), indicated a low passive transcellular transport (Pe = 0.32 ± 0.01 × 10(-6 )cm/s). Using the Caco-2 cell system, the Papp AP-BL in absorptive direction (3.36 ± 0.02 × 10(-5 )cm/s) was significantly higher than the Papp BL-AP in secretive direction (1.75 ± 0.07 × 10(-5 )cm/s), suggesting a polarized transport. The efflux ratio (Papp AP-BL/Papp BL-AP = 0…

The chemistry of melatonin's interaction with reactive species

Melatonin has been shown to be an effective antioxidant in a number of experimental models both in vitro and in vivo. Considering the data available, it is now clear that the indoleamine is involved in antioxidative mechanisms more complex than originally envisaged. These range from the direct radical scavenging of a variety of radicals and reactive species to the control and/or modulation of a number of processes which may trigger a redox imbalance between antioxidant and prooxidant species. This review focuses on the direct radical scavenging activity of melatonin and provides a summary of the mechanisms of the reactions between the indoleamine and reactive species in pure chemical soluti…

Design, synthesis, and biological evaluation of pyridothienotriazolopyrimidine derivatives as new HSP90 inhibitors

Bioactive Compounds and Antioxidant Properties with Involved Mechanisms of Eugenia involucrata DC Fruits

In this study, the phytochemical profile and the antioxidative properties of Eugenia involucrata fruits were evaluated. Spectrophotometric assays indicated that these berries are a rich source of polyphenols with very high radical-scavenging and metal-reducing activities. High-performance liquid chromatography–Orbitrap analysis was able to carry out the annotation of 36 different compounds, mainly belonging to the flavonol, flavan-3-ol, and anthocyanin families. Antioxidant activity of the fruit extract was evaluated in a cell-based lipid peroxidation model. Obtained data showed that the extract, at very low concentration, was able to prevent oxidative damage in HepG2 cells exposed to oxida…

Evolution of Carotenoid Content, Antioxidant Activity and Volatiles Compounds in Dried Mango Fruits (Mangifera Indica L.)

The aim of this research was to study the evolution of carotenoid compounds, antioxidant &beta

Uptake of Betanin and Indicaxanthin by Caco-2 cell monolayer.

Non Invasive RAMAN spectroscopic detection of skin carotenoids in healthy Sicilian subjects.

Antiproliferative Activity Predictor: A New Reliable In Silico Tool for Drug Response Prediction against NCI60 Panel.

In vitro antiproliferative assays still represent one of the most important tools in the anticancer drug discovery field, especially to gain insights into the mechanisms of action of anticancer small molecules. The NCI-DTP (National Cancer Institute Developmental Therapeutics Program) undoubtedly represents the most famous project aimed at rapidly testing thousands of compounds against multiple tumor cell lines (NCI60). The large amount of biological data stored in the National Cancer Institute (NCI) database and many other databases has led researchers in the fields of computational biology and medicinal chemistry to develop tools to predict the anticancer properties of new agents in advan…

Biological Activities of Plant Food Components: Implications in Human Health

Scientific data and epidemiological evidence collected over the last fifty years have shown that nutrition plays a decisive role in human health [...]

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Melatonin is the main secretory product of the pineal gland, and it is involved in the regulation of periodic events. A melatonin production independent of the photoperiod is typical of the gut. However, the local physiological role of melatonin at the intestinal tract is poorly characterized. In this study, we evaluated the anti-inflammatory activities of melatonin in an in vitro model of inflamed intestinal epithelium. To this purpose, we assessed different parameters usually associated with intestinal inflammation using IL-1 beta-stimulated Caco-2 cells. Differentiated monolayers of Caco-2 cells were preincubated with melatonin (1 nmol/L-50 mu mol/L) and then exposed to IL-1 beta. After …

Effect of saffron addition on the microbiological, physicochemical, antioxidant and sensory characteristics of yoghurt

The impact of added saffron on the characteristics of yoghurt was evaluated during storage. The fat content was lower in the saffron yoghurt. All colour variables were significantly affected by saffron and storage. From the 15th day of storage, bacterial numbers in the saffron yoghurt were higher than those of the control yoghurt. Sensory analysis data suggested that colour, odour and texture impacted consistently on the overall acceptability of the saffron yoghurt. Saffron addition significantly increased polyphenol content and antioxidant activity, providing evidence that the enrichment of natural yoghurt with saffron yields an innovative fermented product useful for supplementing antioxi…

Antiproliferative and pro-apoptotic effects of the phytochemical Indicaxanthin on human intestinal (Caco-2) and hepatic (Ha 22T) cancer cell lines

In the present study antiproliferative effects of Indicaxanthin (Ind), a highly bioavailable pigment from the fruits of Opuntia ficus-indica (1), were investigated on a number of human cancer cell lines including hepatocarcinoma cells (HepG2, Ha22T, HUH 7), breast cancer cells (MCF7), cervix epithelial carcinoma (HeLa), and colorectal carcinoma cells (Caco-2). Cytotoxicity of Ind, in a concentration range between 25 to 100 M, was evaluated by Trypan blue exclusion method and MTT assay. Ind caused a clear dose- and time-dependent decrease in the proliferation of Caco-2 and Ha 22T cells with an IC(50) of about 50 M, with minor effect on the other cell lines. Flow cytometric analysis after A…

Tree-Ripe Mango Fruit: Physicochemical Characterization, Antioxidant Properties and Sensory Profile of Six Mediterranean-Grown Cultivars

Some of the key components that contribute to the acceptance of high-quality fresh mangoes by consumers are its flavour, odour, texture and chemical constituents that depend mainly on level of maturity. In the European market, the demand for tree-ripened fruit has increased in recent decades. Nevertheless, the qualitative response and the marketable characteristics of tree-ripened mango fruit grown in the Mediterranean area are not yet studied. Tree-ripened fruits of cv Keitt, Glenn, Osteen, Maya, Kensington Pride and Tommy Atkins were submitted to analytical (fruit weight, transversal diameter, longitudinal diameter, flesh firmness, total soluble solid content, titratable acidity, seed wei…

Protective effect of melatonin against cytotoxic actions of malondialdehyde: an in vitro study on human erythrocytes

Malondialdehyde (MDA), a by-product of the oxidation of polyunsaturated fatty acids, is strongly cytotoxic. Here we report the in vitro ability of melatonin to protect intact human erythrocytes against the damage induced by the exposure to MDA. MDA at 20 microM caused marked variations in the red blood cell (RBC) membrane. High molecular weight fluorescent adducts were formed within minutes with membrane proteins. A 6-hr incubation led to the oxidation of membrane lipids, as reflected by the formation of conjugated diene (CD) lipid hydroperoxides and oxidation of vitamin E, and to an increase of the high molecular weight fluorescent adducts, which were an indication of MDA finally generated…