Binding of 11-cis retinaldehyde to the partially purified cellular retinaldehyde binding protein from bovine retinal pigment epithelium.

11-cis retinaldehyde binding analysis was performed on a bovine retinal pigment epithelium preparation of cellular retinaldehyde binding protein (CRALBP), whose purity degree was estimated as 75%. Equilibrium binding studies were carried out measuring the replacement of tritium-labeled with unlabeled 11-cis retinaldehyde at 25 degrees C. Analysis of the experimental data both by a direct curve-fitting procedure utilizing a non linear least square regression analysis and by a conventional Scatchard plot revealed a single non-interacting binding site with an apparent equilibrium constant of 0.9 X 10(-7) M. A binding stoichiometry of approximately 1 mol of 11-cis retinaldehyde/mol of binding p…

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…

A Deadly Liaison between Oxidative Injury and p53 Drives Methyl-Gallate-Induced Autophagy and Apoptosis in HCT116 Colon Cancer Cells

Methyl gallate (MG), which is a gallotannin widely found in plants, is a polyphenol used in traditional Chinese phytotherapy to alleviate several cancer symptoms. Our studies provided evidence that MG is capable of reducing the viability of HCT116 colon cancer cells, while it was found to be ineffective on differentiated Caco-2 cells, which is a model of polarized colon cells. In the first phase of treatment, MG promoted both early ROS generation and endoplasmic reticulum (ER) stress, sustained by elevated PERK, Grp78 and CHOP expression levels, as well as an upregulation in intracellular calcium content. Such events were accompanied by an autophagic process (16–24 h), where prolonging the …

New Organotin(IV) Compounds: Structural Basis for Antiproliferative Activity and Selectivity

Antioxidative effects of cactus pear (Opuntia ficus indica, L. Mill.) fruits from Sicily and bioavailability of betalain components in healthy humans

Aerobic life is characterised by a steady formation of pro-oxidants, which is approximately balanced by antioxidant defense systems. When cell’s capacity to protect itself fails, oxidative stress occurs. Because of bioactive components vegetables are now considered helpful in preventing chronic pathologies in which oxidative damage is an important etiologic factor. Cactus pear (Opuntia ficus-indica) fruit contains substantial amounts of vitamin C, biothiols, and taurine, and redox-active betalain pigments. It has been shown that a short-term supplementation (500 g fruit pulp daily, 2 wk) positively affected the body’s redox balance, decreased lipid oxidation, and improved antioxidant status…

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

Lipoperoxyl radical scavenging activity of the phytochemical betanin and its aglycone in aqueous/lipid membrane system. Kinetics and mechanistic aspects.

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…

Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages

Macrophages come across active prostaglandin (PG) metabolism during inflammation, shunting early production of pro-inflammatory towards anti-inflammatory mediators terminating the process. This work for the first time provides evidence that a phytochemical may modulate the arachidonate (AA) metabolism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, promoting the ultimate formation of anti-inflammatory cyclopentenone 15deoxy-PGJ2. Added 1 h before LPS, indicaxanthin from Opuntia Ficus Indica prevented activation of nuclear factor-κB (NF-κB) and over-expression of PGE2 synthase-1 (mPGES-1), but up-regulated cyclo-oxygenase-2 (COX-2) and PGD2 synthase (H-PGDS), with final product…

[37] Interactions between vitamin A and vitamin E in liposomes and in biological contexts

Publisher Summary This chapter discusses the interactions between vitamin A and vitamin E in liposomes. The chapter reviews several studies carried out by incorporating a variable proportion of all- trans -retinol and α-tocopherol in soybean phosphatidylcholine liposomes. It discusses the antioxidant effectiveness of all- trans - retinol in retinal membranes, whether deprived of endogenous α-tocopherol. In the experiments discussed in the chapter, synergistic effects between all- trans -retinal and α -tocopherol are evident in chemical bilayer as well as in natural membranes. In addition, when all- trans -retinol and α –tocopherol are allowed to act in combination, consumption of both antio…

Loading and release of the complex [Pt(DTBTA)(DMSO)Cl]Cl·CHCl3 with the 2,2′-dithiobis(benzothiazole) ligand into mesoporous silica and studies of antiproliferative activity on MCF-7 cells

Abstract Synthetic delivery systems have great potential for overcoming problems associated with systemic toxicity that accompanies chemotherapy with the use of cisplatin and family of platinum anticancer drugs. Mesoporous silicates have been studied in context of drug delivery and drug targeting. In this paper we report the studies of loading and release of a platinum complex, [Pt(DTBTA)(DMSO)Cl]Cl∙CHCl3 (1) where DTBTA = 2,2′-dithiobis(benzothiazole), that was recently synthesized and structurally characterized. Evaluation in vitro of antitumor activity against a human breast cancer cell line (MCF-7) showed a very potent activity of complex(1). Therefore, we thought to incorporate this co…

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…

Betanin inhibits myeloperoxidase/nitrite-mediated peroxidation of human low density lipoprotein

Mechanism of action of the betalain pigment indicaxanthin, purified from fruits of Opuntia ficus-indica, on mouse ileal motility in vitro.

Antioxidant activities of sicilian prickly pear (Opuntia ficus indica) fruit extracts and reducing properties of its betalains: betanin and indicaxanthin.

Sicilian cultivars of prickly pear (Opuntia ficus indica) produce yellow, red, and white fruits, due to the combination of two betalain pigments, the purple-red betanin and the yellow-orange indicaxanthin. The betalain distribution in the three cultivars and the antioxidant activities of methanolic extracts from edible pulp were investigated. In addition, the reducing capacity of purified betanin and indicaxanthin was measured. According to a spectrophotometric analysis, the yellow cultivar exhibited the highest amount of betalains, followed by the red and white ones. Indicaxanthin accounted for about 99% of betalains in the white fruit, while the ratio of betanin to indicaxanthin varied fr…

The effects of glucocorticoids on thymidine kinase and nucleoside phosphotransferase during development of chicken embryo retina.

AbstractThymidine kinase in chick embryo retina reaches its highest values on the 8–10th day of development, then declines reaching the lowest value at hatching. The rate of DNA synthesis essentially follows this activity while, in contrast, nucleoside phosphotransferase increases progressively during development. Glucocorticoids at 5 × 10−6M lower the level of thymidine kinase in isolated retinas of chick embryo. The most effective steroid was hydrocortisone. The effect was observed in retinas from 8–18-day-old chick embryo and, except on the 18th day, was always of the same magnitude. We suggest that a glucocorticoid can be the natural factor responsible for the marked fall in thymidine k…

Antioxidant activities of prickly pear ( Opuntia ficus indica) fruits and its betalains: betanin and indicaxanthin.

Phytochemicals and phytomedicines are now an expanding research fields. A great number of active agents occurring in plants and herbs have been discovered, which is fundamental to find a rationale for the health effects of these herbs, in many cases used for centuries as traditional remedies. The knowledge of the mechanisms and molecular basis of their action is the final objective to understand the mode of action of the discovered principles. Studies on the bioactivity of cactus pear are very recent and results obtained so far, while exciting, now generate new questions. In vivo studies on healthy humans showed a strong protection of the body antioxidant system, and a marked reduction of p…

Apoptotic effect of a phytosterol-ingredient and its main phytosterol (β-sitosterol) in human cancer cell lines

Dietary interventions may effectively control cancer development, with phytosterols (PS) being a class of cancer chemopreventive dietary phytochemicals. The present study, for the first time, evaluates the antiproliferative effects of a PS-ingredient used for the enrichment of several foods and its main PS, β-sitosterol, at physiological serum levels, in the most prevalent cancer cells in women (breast (MCF-7), colon (HCT116) and cervical (HeLa)). In all three cell lines, these compounds induced significant cell viability reduction without a clear time- and dose-dependent response. Moreover, all treatments produced apoptotic cell death with the induction of DNA fragmentation through the app…

Redox Properties, Bioactivity and Health Effects of Indicaxanthin, a Bioavailable Phytochemical from Opuntia ficus indica, L.: A Critical Review of Accumulated Evidence and Perspectives

Phytochemicals from plant foods are considered essential to human health. Known for their role in the adaptation of plants to their environment, these compounds can induce adaptive responses in cells, many of which are directed at maintaining the redox tone. Indicaxanthin is a long-known betalain pigment found in the genus Opuntia of cactus pear and highly concentrated in the edible fruits of O. ficus indica, L. whose bioactivity has been overlooked until recently. This review summarizes studies conducted so far in vitro and in vivo, most of which have been performed in our laboratory. The chemical and physicochemical characteristics of Indicaxanthin are reflected in the molecule’s reducing…

Synthesis and Antioxidative Properties of 1,2,3,4-Tetrahydropyridine Derivatives with Different Substituents in 4-Position

Natural products are an excellent source of inspiration for the development of new drugs. Among them, betalains have been extensively studied for their antioxidant properties and potential application as natural food dyes. Herein, we describe the seven-step synthesis of new betalamic acid analogs without carboxy groups in the 2- and 6-position with an overall yield of ~70%. The Folin–Ciocalteu assay was used to determine the antioxidant properties of protected intermediate 21. Additionally, the five-step synthesis of betalamic acid analog 35 with three ester moieties was performed. Using NMR techniques, the stability of the obtained compounds towards oxygen was analyzed.

Oral supplements of vitamin E improve measures of oxidative stress in plasma and reduce oxidative damage to LDL and erythrocytes in β-thalassemia intermedia patients

Fifteen beta-thalassemia intermedia patients, not requiring chronic transfusional therapy, were monitored in order to check their antioxidant status, and the lipid oxidation products in plasma, LDL, and erythrocytes before and during a 9-month oral treatment with 600 mg/day vitamin E. The low level of vitamin E, and high level of malondialdehyde in plasma clearly tended to normalize after three months (P < .001), and were quite similar to control after six months. The abnormally low level of vitamin E in LDL and the four times higher than control basal level of conjugated dienes (LDL-CD), were not modified after three months of treatment. Significant changes of LDL-VE (P < .05) and of the b…

Synthesis, spectroscopic characterization and antiproliferative activity of two platinum(II) complexes containing N-donor heterocycles

Abstract Novel mononuclear complexes of Pt(II), cis -[PtCl 2 (DMSO)HL]·2DMSO ( 1 ), where HL = 7-amino-2-(methylthio)[1,2,4]triazolo[1,5- a ]pyrimidine-6-carboxylic acid and Pt(bdt)Cl 2 ( 2 ), where bdt = [2,4-bis(5,6-diphenyl-1,2,4-triazin-3yl)-pyridine] have been synthesized and characterized by elemental analysis, IR and 1 H NMR spectroscopy and X-ray crystallography diffraction analyses. The molecular structure of ( 1 ) shows that Pt(II) ion has a square planar geometry with N(3) bonded heterocycle ligand, two cis chloride anions and S-bonded dimethylsulfoxide. The antiproliferative activity of complexes ( 1 ) and ( 2 ) has been tested in vitro against HepG2 human hepatoma cells and non…

Antiproliferative effect of main dietary phytosterols and/or b-cryptoxanthin in human colon cancer Caco-2 cells through cytosolic Ca+2-and oxidative stress-induced apoptosis

The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis

Combining phytochemicals with chemotherapics is an emerging strategy to treat cancer to overcome drug toxicity and resistance with natural compounds. We assessed the effects of indicaxanthin (Ind), a pigment obtained from Opuntia ficus-indica (L. Mill) fruit, combined with cisplatin (CDDP) against cervical cancer cells (HeLa). Measured cell viability via Trypan blue assay

Aza-isoindolo and isoindolo-azaquinoxaline derivatives with antiproliferative activity

Abstract Three new ring systems, pyrido[2′,3′:3,4]pyrrolo[1,2- a ]quinoxalines, pyrido[3′,2′:3,4]pyrrolo[1,2- a ]quinoxalines and pyrido[2′,3′:5,6]pyrazino[2,1- a ]isoindoles, were synthesized through an aza-substitution on the already active isoindolo-quinoxaline system and in particular in the position 7 or 4 of the isoindole moiety and in position 5 of the quinoxaline portion. All new compounds were screened by the National Cancer Institute (Bethesda, MD) against a panel of 60 human tumor cell lines. Biological results of the most active derivatives, with pGI 50 values between 7.09 and 7.27, confirmed the importance of the presence of methoxy substituents for biological activity. The ant…

Oxidative stress after moderate to extensive burning in humans.

Lipid peroxidation products, lipid antioxidants, and hematologic and blood chemistry changes were evaluated in plasma of patients after acute burning injury involving 10% (n=8), 20% (n=8), and 40% (n=5) of total body surface area (TBSA), 24 h after burning (baseline) up to 30 days after. Markedly increased plasma levels of malondialdehyde (MDA) were observed at baseline in all patients, according to the extent of the injury, then the values declined progressively. However, levels of MDA remained above normal up to 30 days even in less injured patients. On the other hand, the plasma level of conjugated diene lipid hydroperoxides was only slightly higher than control at the baseline, then dro…

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…

ATTIVITA’ CITOTOSSICA DI COMPLESSI ORGANOSTAGNO(IV) CON TRIAZOLOPIRIMIDINE CONTENENTI ATOMI DI OSSIGENO ESOCICLICO

Le triazolopirimidine sono leganti eterociclici di crescente interesse. I composti di organostagno(IV) sono caratterizzati dalla presenza di un atomo di stagno (Sn) legato covalentemente ad uno o più sostituenti organici. In questo studio1 sono stati sintetizzati: Me3Sn(5tpO)(1); n-Bu3Sn(5tpO)(2); Me3Sn(mtpO)(3); n-Bu3Sn(mtpO)(4); n-Bu3Sn(HtpO2)(5); Ph3Sn(HtpO2)(6) e la loro citotossicità valutata su tre differenti linee cellulari tumorali umane: HCT-116 (carcinoma del colon retto), HepG2 (epatocarcinoma) e MCF-7 (carcinoma mammario). I complessi 2, 4, 5 e 6 hanno mostrato attività citotossica di 1-2 ordini di grandezza superiore al cis-platino, sulle 3 linee cellulari tumorali. Il meccanis…

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…

Effects of Plant Sterols or β-Cryptoxanthin at Physiological Serum Concentrations on Suicidal Erythrocyte Death.

The eryptotic and hemolytic effects of a phytosterol (PS) mixture (β-sitosterol, campesterol, stigmasterol) or β-cryptoxanthin (β-Cx) at physiological serum concentration and their effect against oxidative stress induced by tert-butylhydroperoxide (tBOOH) (75 and 300 μM) were evaluated. β-Cryptoxanthin produced an increase in eryptotic cells, cell volume, hemolysis, and glutathione depletion (GSH) without ROS overproduction and intracellular Ca2+influx. Co-incubation of both bioactive compounds protected against β-Cx-induced eryptosis. Under tBOOH stress, PS prevented eryptosis, reducing Ca2+influx, ROS overproduction and GSH depletion at 75 μM, and hemolysis at both tBOOH concentrations. β…

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 …

Antioxidant Activity of All-trans-retinol in Homogeneous Solution and in Phosphatidylcholine Liposomes

A kinetic quantification of the lipoperoxyl radical-scavenging activity of all-trans-retinol has been carried out in homogeneous solution, when radicals were produced from the oxidation of methyl linoleate in methanol, initiated by the lipid-soluble 2,2′-azobis (2,4-dimethyl-valeronitrile) (AMVN) as well as in a soybean phosphatidylcholine membrane model, in which peroxidation was induced either by AMVN or the hydrophylic 2,2′-azobis(2-amidinopropane)hydrochloride (AAPH). The physical microenvironment contributes to the determination of antioxidant efficiency of all-trans-retinol. In homogeneous solution the kinetic constant kinh is 3.5 × 105 M-1 s-1 and appears of the same order of magnitu…

Inhibition of the mechanical activity of mouse ileum by cactus pear (Opuntia Ficus Indica, L, Mill.) fruit extract and its pigment indicaxanthin.

We investigated, using an organ bath technique, the effects of a hydrophilic extract from Opuntia ficus indica fruit pulp (cactus fruit extract, CFE) on the motility of mouse ileum, and researched the extract component(s) responsible for the observed responses. CFE (10-320 mg of fresh fruit pulp equivalents/mL of organ bath) reduced dose-dependently the spontaneous contractions. This effect was unaffected by tetrodotoxin, a neuronal blocker, N(omega)-nitro-l-arginine methyl ester, a nitric oxide synthase blocker, tetraethylammonium, a potassium channel blocker, or atropine, a muscarinic receptor antagonist. CFE also reduced the contractions evoked by carbachol, without affecting the contrac…

Melatonin protects human red blood cells from oxidative hemolysis: new insights into the radical-scavenging activity.

Antioxidant activity of melatonin in human erythrocytes, exposed to oxidative stress by cumene hydroperoxide (cumOOH), was investigated. CumOOH at 300 microM progressively oxidized a 1% suspension of red blood cells (RBCs), leading to 100% hemolysis in 180 min. Malondialdehyde and protein carbonyls in the membrane showed a progressive increase, as a result of the oxidative damage to membrane lipids and proteins, reaching peak values after 30 and 40 min, respectively. The membrane antioxidant vitamin E and the cytosolic reduced glutathione (GSH) were totally depleted in 20 min. As a consequence of the irreversible oxidative damage to hemoglobin (Hb), hemin accumulated into the RBC membrane d…

Proeryptotic Activity of 4-Hydroxynonenal: A New Potential Physiopathological Role for Lipid Peroxidation Products

Background: Eryptosis is a physiological, apoptosis-like death of injured erythrocytes crucial to prevent premature haemolysis and the pathological sequalae generated by cell-free haemoglobin. When dysregulated, the process is associated to several inflammatory-based pathologies. 4-Hydroxy-trans-2-nonenal (HNE) is an endogenous signalling molecule at physiological levels and, at higher concentrations, is involved in the pathogenesis of several inflammatory-based diseases. This work evaluated whether HNE could induce eryptosis in human erythrocytes. Methods: Measurements of phosphatidylserine, cell volume, intracellular oxidants, Ca++, glutathione, ICAM-1, and ceramide were assessed by flow …

Amyloid-Beta Induces Different Expression Pattern of Tissue Transglutaminase and Its Isoforms on Olfactory Ensheathing Cells: Modulatory Effect of Indicaxanthin

Abstract Alzhèimer Disease (AD) is characterized by protein aggregates in the brain, including amyloid-beta (Aβ), a substrate for tissue transglutaminase (TG2). We assessed the effect of full native peptide of Aβ (1–42), the fragments (25–35 and 35–25) on TG2 expression and its isoforms (Long and Short) on mouse Olfactory Ensheathing Cells (OECs). The levels of cytoskeletal proteins, Vimentin and Glial Fibrillary Acid Protein, were also studied. The effect of the pre-treatment with Indicaxanthin on cell viability, total Reactive Oxygen Species, superoxide anion and apoptotic pathway activation was assessed. Since Nestin is co-expressed in pluripotent stem cells with cyclin D1, their levels …

Indicaxanthin from Opuntia ficus indica (L. Mill) Inhibits Oxidized LDL-Mediated Human Endothelial Cell Dysfunction through Inhibition of NF-κB Activation

Oxidized low-density lipoproteins (oxLDL) play a pivotal role in the etiopathogenesis of atherosclerosis through the activation of inflammatory signaling events eventually leading to endothelial dysfunction and senescence. In the present work, we investigated the effects of indicaxanthin, a bioavailable, redox-modulating phytochemical from Opuntia ficus indica fruits, with anti-inflammatory activity, against oxLDL-induced endothelial dysfunction. Human umbilical vein cord cells (HUVEC) were stimulated with human oxLDL, and the effects of indicaxanthin were evaluated in a range between 5 and 20 μM, consistent with its plasma level after a fruit meal (7 μM). Pretreatment with indicaxanthin si…

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…

Betanin inhibits the myeloperoxidase/nitrite-induced oxidation of human low-density lipoproteins

Production of nitrogen dioxide by the activity of myeloperoxidase (MPO) in the presence of nitrite is now considered a key step in the pathophysiology of low-density lipoprotein (LDL) oxidation. This study shows that betanin, a phytochemical of the betalain class, inhibits the production of lipid hydroperoxides in human LDL submitted to a MPO/nitrite-induced oxidation. Kinetic measurements including time-course of particle oxidation and betanin consumption, either in the presence or in the absence of nitrite, suggest that the antioxidant effect is possibly the result of various actions. Betanin scavenges the initiator radical nitrogen dioxide and can also act as a lipoperoxyl radical-scaven…

Composizione comprendente indicaxantina per uso per la prevenzione e il trattamento del diabete mellito di tipo 2, obesità, stress ossidativo e patologie infiammatorie.

Exposure to malondialdehyde induces an early redox unbalance preceding membrane toxicity in human erythrocytes.

This work investigated the oxidative injury to human red blood cells (RBCs) by the exposure to exogenous malondialdehyde (MDA), in a physiological environment. When a 10% RBC suspension was incubated in autologous plasma, in the presence of 50 microM MDA, 30% of MDA entered into the cells. A time-course study showed that MDA caused early (30-120 min) and delayed (3-18 h) effects. MDA caused a fast depletion of reduced glutathione, and loss of the glucose-6-phosphate dehydrogenase activity, followed by a decrease of HbO2. Accumulation of methemoglobin, and formation of small amounts of hemichrome were later evident. Also, an HbO2-derived fluorescent product was measured in the membrane. The …

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

Synthesis and antiproliferative activity of thiazolyl-bis-pyrrolo[2,3-b]pyridines and indolyl-thiazolyl-pyrrolo[2,3-c]pyridines, nortopsentin analogues.

Two new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and indole units were both substituted by 7-azaindole moieties or one indole unit was replaced by a 6-azaindole portion, were efficiently synthesized. Compounds belonging to both series inhibited the growth of HCT-116 colorectal cancer cells at low micromolar concentrations, whereas they did not affect the viability of normal-like intestinal cells. A compound of the former series induced apoptosis, evident as externalization of plasma membrane phosphatidylserine (PS), and changes of mitochondrial trans-membrane potential, while blocking the cell cycle in G2/M phase. In contr…

Anti-cancer activity of di- and tri-organotin(IV) compounds with D-(+)-Galacturonic acid on human tumor cells

Abstract We have compared the anti-proliferative activity in vitro, of R2SnGala (1-3) [R = Me, n-Bu, Ph] and novel R3SnGala (4, 5) [R = Me, n-Bu] with D-(+)-Galacturonic acid [HGala; Galaq-, q = (2) and (1) for R2SnGala and R3SnGala, respectively] compounds, towards human tumor cell lines of intestinal carcinoma (HCT-116) and breast adenocarcinoma (MCF-7). The new synthesized 4 and 5 compounds were characterized, in solution, by 1H, 13C and 119Sn NMR, that showed that HGala acts as monoanionic moiety and evidenced the dynamic behavior of the compounds, due to inter-conversions involving the anomeric carbon atom of the ligand. Cell viability, apoptosis induction and cell cycle distribution w…

Synthesis and Antitumor Activity of New Thiazole Nortopsentin Analogs

New thiazole nortopsentin analogs in which one of the two indole units was replaced by a naphthyl and/or 7-azaindolyl portion, were conveniently synthesized. Among these, three derivatives showed good antiproliferative activity, in particular against MCF7 cell line, with GI50 values in the micromolar range. Their cytotoxic effect on MCF7 cells was further investigated in order to elucidate their mode of action. Results showed that the three compounds act as pro-apoptotic agents inducing a clear shift of viable cells towards early apoptosis, while not exerting necrotic effects. They also caused cell cycle perturbation with significant decrease in the percentage of cells in the G0/G1 and S ph…

Oxidative Modification of Low-Density Lipoprotein and Atherogenetic Risk in β-Thalassemia

AbstractWe investigated the oxidative state of low-density lipoprotein (LDL) in patients with β-thalassemia to determine whether there was an association with atherogenesis. Conjugated diene lipid hydroperoxides (CD) and the level of major lipid antioxidants in LDL, as well as modified LDL protein, were evaluated in 35 β-thalassemia intermedia patients, aged 10 to 60, and compared with age-matched healthy controls. Vitamin E and β-carotene levels in LDL from patients were 45% and 24% of that observed in healthy controls, respectively. In contrast, the mean amount of LDL-CD was threefold higher and lysil residues of apo B-100 were decreased by 17%. LDL-CD in thalassemia patients showed a str…

Modulation by docosahexaenoic acid of the epinephrine-stimulated adenylate cyclase activity of the bovine retina.

This work shows that unsaturated fatty acids enhance the epinephrine-stimulated adenylate cyclase activity in bovine retina. The modulating effect on the epinephrine-stimulated formation of cyclic AMP seems to be linked to the degree of unsaturation of the fatty acid. Treatment of the intact retina with docosahexaenoic acid in the concentration range 0.5 X 10(-6)-1 X 10(-3) M does not affect the enzyme activity measured in the absence of the hormone but markedly increases the cyclase activity when the tissue is incubated in the presence of 0.1 mM epinephrine. Docosahexaenoic acid enhances the maximal response to epinephrine without affecting the apparent ED50 value for this effector. Docosa…

Oxidation resistance of LDL is correlated with vitamin E status in beta-thalassemia intermedia.

The alteration of the oxidant/antioxidant balance may affect the susceptibility of low density lipoproteins (LDL) to oxidation in haemolytic disorders such as thalassemia. Thirty patients affected by beta-thalassemia intermedia were examined, and compared with age-matched healthy controls. The mean amount of vitamin E in the thalassemic LDL was lower than control (p0.0001), either when it was calculated on the base of LDL protein (61% decrease) or cholesterol (25% decrease). The LDL resistance to Cu2+-induced oxidation, evaluated as the length of the lag phase before the onset of conjugated diene (CD) lipid hydroperoxide production, was 20% lower than control. Other parameters of LDL suscep…

Short-term cactus pear [

Background: Dietary ingredients and food components are major modifiable factors protecting immune system and preventing the progression of a low-grade chronic inflammation responsible for age-related diseases. Objective: Our study explored whether cactus pear (Opuntia ficus-indica, Surfarina cultivar) fruit supplementation modulates plasma inflammatory biomarkers in healthy adults. Correlations between inflammatory parameters and antioxidant status were also assessed in parallel. Design: In a randomised, 2-period (2 weeks/period), crossover, controlled-feeding study, conducted in 28 healthy volunteers [mean age 39.96 (±9.15) years, BMI 23.1 (±1.5) kg/m2], the effects of a diet supplemented…

Cytoprotective effects of indicaxanthin in beta-thalassemia red blood cells

Betanin protects endothelial cell dysfunction produced by activated HL-60

Phenolic Composition of Hydrophilic Extract of Manna from Sicilian Fraxinus angustifolia Vahl and its Reducing, Antioxidant and Anti-Inflammatory Activity in Vitro

Manna, a very singular vegetable product derived from the spontaneous solidification of the sap of some Fraxinus species, has long been known for its mild laxative and emollient properties. In this work, a hydro-alcoholic extract of manna (HME) from Sicilian Fraxinus angustifolia Vahl was investigated using HPLC-DAD to find phenol components and using chemical and biological in vitro assays to determine its reducing, antioxidant and anti-inflammatory capacity. We identified elenolic acid, tyrosol, hydroxytyrosol, catechin, fraxetin, verbascoside, gallic acid, procyanidin-B1, and luteolin 3,7 glucoside, in order of abundance. Measurements of total antioxidant activity by Folin-Ciocalteu reac…

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

Quality characteristic and in vitro digestibility study of barley flour enriched ditalini pasta

Redox and autonomic responses to acute exercise-post recovery following Opuntia ficus-indica juice intake in physically active women

Background: The aim of this study was to investigate if the supplementation with Opuntia ficus-indica (OFI) juice may affect plasma redox balance and heart rate variability (HRV) parameters following a maximal effort test, in young physically active women. Methods: A randomized, double blind, placebo controlled and crossover study comprising eight women (23.25 ± 2.95 years, 54.13 ± 9.05 kg, 157.75 ± 0.66 cm and BMI of 21.69 ± 0.66 kg/m2) was carried out. A juice containing OFI diluted in water and a Placebo solution were supplied (170 ml; OFI = 50 ml of OFI juice + 120 ml of water; Placebo = 170 ml beverage without Vitamin C and indicaxanthin). Participants consumed the OFI juice or Placebo…

Indicaxanthin from Opuntia Ficus Indica (L. Mill) impairs melanoma cell proliferation, invasiveness, and tumor progression.

Abstract Background: A strong, reciprocal crosstalk between inflammation and melanoma has rigorously been demonstrated in recent years, showing how crucial is a pro-inflammatory microenvironment to drive therapy resistance and metastasis. Purpose: We investigated on the effects of Indicaxanthin, a novel, anti-inflammatory and bioavailable phytochemical from Opuntia Ficus Indica fruits, against human melanoma both in vitro and in vivo. Study Design and Methods: The effects of indicaxanthin were evaluated against the proliferation of A375 human melanoma cell line and in a mice model of cutaneous melanoma. Cell proliferation was assessed by MTT assay, apoptosis by Annexin V-Fluorescein Isothio…

Synthesis, structural characterization, anti-proliferative and antimicrobial activity of binuclear and mononuclear Pt(II) complexes with perfluoroalkyl-heterocyclic ligands

Abstract In this paper we report the synthesis of four Pt(II) complexes with 5-perfluoroalkyl-1,2,4-oxadiazolyl-pyridine and 3-perfluoroalkyl-1-methyl-1,2,4-triazolyl-pyridine ligands. Two binuclear complexes [PtCl(pfibap)2](µ-Cl)2 (1), [Pt2(µ-Cl)2(pfioap)4]Cl2 (2), and two mononuclear [PtCl2(pfptp)] (3), [PtCl2(pfhtp)2] (4), were synthesized with the ligands: 2-(5-perfluoropropyl)-1,2,4-oxadiazole-3yl)-pyridine (pfpop), 2-(5-perfluoroheptyl-1,2,4-oxadiazole-3yl)-pyridine (pfhop), 2-(3-perfluoropropyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfptp), 2-(3-perfluoroheptyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfhtp), and were structurally characterized. All complexes were tested in vitro on th…

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…

A Mixture of Dietary Plant Sterols at Nutritional Relevant Serum Concentration Inhibits Extrinsic Pathway of Eryptosis Induced by Cigarette Smoke Extract

Cell death program of red blood cells (RBCs), called eryptosis, is characterized by activation of caspases and scrambling of membrane phospholipids with externalization of phosphatidylserine (PS). Excessive eryptosis confers a procoagulant phenotype and is implicated in impairment of microcirculation and increased prothrombotic risk. It has recently been reported that cigarette smokers have high levels of circulating eryptotic erythrocytes, and a possible contribution of eryptosis to the vaso-occlusive complications associated to cigarette smoke has been postulated. In this study, we demonstrate how a mixture of plant sterols (MPtS) consisting of β-sitosterol, campesterol and stigmasterol, …

Synthesis, antitumor activity and CDK1 inhibiton of new thiazole nortopsentin analogues

A new series of thiazole nortopsentin analogues was conveniently synthesized with fair overall yields. The antiproliferative activity of the new derivatives was tested against different human tumor cell lines of the NCI full panel. Four of them showed good antitumor activity with GI(50) values from micro to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and DNA fragmentation. The most active and selective of the new thiazoles confined viable cells in G2/M phase and markedly inhibited in vitro CDK1 activity. (C) 2017 Elsevier Masson SAS.

Cactus Pear Fruit Extract exerts anti-inflammatory effects on carrageenan-induced rat pleurisy.

Evaluation of the IKKβ Binding of Indicaxanthin by Induced-Fit Docking, Binding Pose Metadynamics, and Molecular Dynamics

Background: Indicaxanthin, a betaxanthin belonging to the betalain class of compounds, has been recently demonstrated to exert significant antiproliferative effects inducing apoptosis of human melanoma cells through the inhibition of NF-κB as the predominant pathway. Specifically, Indicaxanthin inhibited IκBα degradation in A375 cells. In resting cells, NF-κB is arrested in the cytoplasm by binding to its inhibitor protein IκBα. Upon stimulation, IκBα is phosphorylated by the IKK complex, and degraded by the proteasome, liberating free NF-κB into the nucleus to initiate target gene transcription. Inhibition of the IKK complex leads to the arrest of the NF-κB pathway.Methods: To acquire deta…

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

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Recently, we have shown anti-proliferative and pro-apoptotic effects of indicaxanthin associated with epigenetic modulation of the onco-suppressor &lt;i&gt;p16&lt;/i&gt;&lt;sup&gt;&lt;i&gt;INK4a&lt;/i&gt;&lt;/sup&gt; 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. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; 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…

Indicaxanthin and betanin suppress LPS-induced NF-kB activation and modulate the levels of inflammatory mediators iNOS, COX-2 and PGE2 in macrophages

Indicaxanthin up-regulates COX-2 gene and increases cyclopentenone levels in LPS-activated RAW264.7 macrophages.

Cross-talk between minimally primed HL-60 cells and resting HUVEC reveals a crucial role for adhesion over extracellularly released oxidants

This study demonstrates that a long-lasting co-culture of neutrophil surrogates (HL-60 cells), minimally primed by platelet activating factor (PAF), and resting endothelial cells (EC) results in the elaboration of an hyper-adhesive endothelial surface, as measured by the increase in the expression of endothelial adhesion molecules E-Selectin, VCAM-1, and ICAM-1. This endothelial dysfunction is mediated by the activation of the redox-sensitive transcription factor NF-κB through an exclusive adhesion-driven mechanism active in the endothelial cell: reactive oxygen and nitrogen species, extracellularly released by minimally primed HL-60 cells, are not involved in the induction of the endotheli…

The diet phytochemical Indicaxanthin suppresses 7-ketocholesterol-induced THP-1 cell apoptosis via inhibition of redox unbalance, cytosolic Ca2+ increase and NF-kB activation.

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 …

Dietary indicaxanthin from cactus pear (Opuntia ficus-indica L. Mill) fruit prevents eryptosis induced by oxysterols in a hypercholesterolaemia-relevant proportion and adhesion of human erythrocytes to endothelial cell layers.

Toxic oxysterols in a hypercholesterolaemia-relevant proportion cause suicidal death of human erythrocytes or eryptosis. This process proceeds through early production of reactive oxygen species (ROS), release of prostaglandin (PGE2) and opening of PGE2-dependent Ca channels, membrane phosphatidylserine (PS) externalisation, and cell shrinkage. The present study was the first to reveal that a bioavailable phytochemical, indicaxanthin (Ind) from cactus pear fruit, in a concentration range (1·0–5·0 μM) consistent with its plasma level after a fruit meal, prevents PS externalisation and cell shrinkage in a dose-dependent manner when incubated with isolated healthy human erythrocytes exposed to…

7-Keto-Cholesterol and Cholestan-3beta, 5alpha, 6beta-Triol Induce Eryptosis through Distinct Pathways Leading to NADPH Oxidase and Nitric Oxide Synthase Activation

Background/aims We showed that patho-physiological concentrations of either 7-keto-cholesterol (7-KC), or cholestane-3beta, 5alpha, 6beta-triol (TRIOL) caused the eryptotic death of human red blood cells (RBC), strictly dependent on the early production of reactive oxygen species (ROS). The goal of the current study was to assess the contribution of the erythrocyte ROS-generating enzymes, NADPH oxidase (RBC-NOX), nitric oxide synthase (RBC-NOS) and xanthine oxido-reductase (XOR) to the oxysterol-dependent eryptosis and pertinent activation pathways. Methods Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, reactive oxygen/nitrogen species (RONS) and nitri…

Vitamin A Inhibits Doxorubicin-Induced Membrane Lipid Peroxidation in Rat Tissues in Vivo

The antioxidant activity of vitamin A against lipid peroxidation induced by doxorubicin in rat tissues in vivo was investigated. A single ip injection of doxorubicin (30 mg/kg body wt) markedly raised the level of peroxidated lipids measured as TBARS and conjugated dienes in heart and brain membrane preparations. Other tissues, such as retina and liver, did not show any increase of lipid peroxides over control values. Pretreatment of rats with two daily subcutaneous injections of retinol palmitate (0.25 g/kg body wt), for 2 days, before injecting doxorubicin, inhibited peroxidation of heart and brain membrane lipids. The antioxidant action of vitamin A does not appear to be mediated by enha…

Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts

Several studies have recently investigated the role of nutraceuticals in complex pathophysiological processes such as oxidative damages, inflammatory conditions and excitotoxicity. In this regard, the effects of nutraceuticals on basic functions of neuronal cells, such as excitability, are still poorly investigated. For this reason, the possible modulation of neuronal excitability by phytochemicals (PhC) could represent an interesting field of research given that excitotoxicity phenomena are involved in neurodegenerative alterations leading, for example, to Alzheimer's disease. The present study was focused on indicaxanthin from Opuntia ficus indica, a bioactive betalain pigment, with a pro…

Indicaxanthin from Opuntia ficus-indica Fruit Ameliorates Glucose Dysmetabolism and Counteracts Insulin Resistance in High-Fat-Diet-Fed Mice

Obesity-related dysmetabolic conditions are amongst the most common causes of death globally. Indicaxanthin, a bioavailable betalain pigment from Opuntia ficus-indica fruit, has been demonstrated to modulate redox-dependent signalling pathways, exerting significant anti-oxidative and anti-inflammatory effects in vitro and in vivo. In light of the strict interconnections between inflammation, oxidative stress and insulin resistance (IR), a nutritionally relevant dose of indicaxanthin has been evaluated in a high-fat diet (HFD) model of obesity-related IR. To this end, biochemical and histological analysis, oxidative stress and inflammation evaluations in liver and adipose tissue were carried…

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

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…

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

Complessi di Platinum(II): sintesi, studi di DNA-binding e loro attività antitumorale in vitro

Con lo scopo di trovare nuovi analoghi del Cis-DDP (cis-diammino dicloro platino(II)) nuovi complessi del platino sono stati sintetizzati, caratterizzati e ne è stata studiata l’attività antitumorale in vitro [1]. Recentemente sono stati preparati complessi con metalli del quarto periodo di transizione con entrambi i leganti, dipirido[3,2-a:2’,3’-c]fenazina (dppz) e glicinato (gly) [2]. I composti di nuova sintesi vengono generalmente caratterizzati attraverso parecchie tecniche analitiche incluso la cristallografia a raggi-X e la loro attività antitumorale viene testata su un vasto pannello di linee cellulari umane [1,2]. Le proprietà biologiche spesso sono correlate alla loro interazione …

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

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

In Vitro Bioavailability of Phenolic Compounds from Five Cultivars of Frozen Sweet Cherries (Prunus aviumL.)

The bioavailability of phenolic compounds from five cultivars of frozen sweet cherries was assessed by a digestion process involving pepsin-HCl digestion (to simulate gastric digestion) and pancreatin digestion with bile salts (to simulate small intestine conditions) and dialyzed to assess serum- and colon-available fractions. After pepsin digestion, the % recovery of total phenolics, relative to the original starting material, increased, whereas the % anthocyanins did not change. Following pancreatic digestion and dialysis, the total phenolics in the IN (serum-available) fraction was about 26–30% and the OUT (colon-available) fraction was about 77–101%. The anthocyanin content in the IN fr…

Supplementation with cactus pear (Opuntia ficus-indica) fruit decreases oxidative stress in healthy humans: a comparative study with vitamin C.

Background: Cactus pear (Opuntia ficus-indica) fruit contains vitamin C and characteristic betalain pigments, the radical-scavenging properties and antioxidant activities of which have been shown in vitro. Objective: We investigated the effects of short-term supplementation with cactus pear fruit compared with vitamin C alone on total-body oxidative status in healthy humans. Design: In a randomized, crossover, double-treatment study, 18 healthy volunteers received either 250 g fresh fruit pulp or 75 mg vitamin C twice daily for 2 wk, with a 6-wk washout period between the treatments. Before (baseline) and after each treatment, 8-epiprostaglandin F2α (8-epi-PGF2α) and malondialdehyde in plas…

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…

[39] Lipoperoxyl radical-scavenging activity of vitamin A and analogs in homogeneous solution

Publisher Summary This chapter describes the assay method for determining the reactivity of all- trans -retinol and other natural and synthetic retinoids, with radicals generated by reaction of the lipid-soluble azo initiator 2,2 ' -azobis(2,4-dimethylvaleronitrile) (AMVN) with methyl linoleate. The chapter discusses the general principles for measuring antioxidant activity. The oxidation of linoleic acid methyl ester (LAME) is the simplest model for studying the oxidation of polyunsaturated lipids and has been widely adopted to evaluate antioxidant activity. Because linoleic acid has two double bonds, peroxidation occurs at the bisallylic hydrogens and generates conjugated diene hydroperox…

New 1,2,4-oxadiazole nortopsentin derivatives with cytotoxic activity

New analogs of nortopsentin, a natural 2,4-bis(3&prime

Modulation of TH1/TH17 equilibrium in vitro by indicaxanthin from Opuntia ficus indica (L. Mill)

Indicaxanthin, Th1

Lipoperoxyl radical scavenging and antioxidative effects of red beet pigments

Nucleoside phosphotransferase in animal tissues

Spectrophotometric evidence for the solubilization site of betalain pigments in membrane biomimetic systems.

The solubilization site of two betalain pigments, namely, betanin and indicaxantin, into l-alpha-dipalmitoyl-phosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) vesicles was investigated by a spectrophotometric study. Pigment absorbance was monitored by varying phospholipid concentration, at a constant temperature that was varied in a range including the main phase transition temperature (Tm) of the relevant phospholipid bilayer. Maximum betanin absorption increased with the increase of DPPC concentration within the entire temperature range, reaching a plateau. The binding constant (Kb) of the pigment, calculated according to a pseudo-two-phase model, varied with the temper…

Monofloral honeys by Sicilian black honeybee (Apis mellifera ssp. sicula) have high reducing power and antioxidant capacity

Thirty samples from thirteen Sicilian monofloral honeys by the local black honeybee, and two honeydew honeys, were studied to assess phenol content, reducing power and antioxidant capacity as well as correlations among these parameters. Honeys from Apiaceae showed the highest phenol amount and capacity to reduce ferric ion and stable chemical radicals, whereas honeys from Leguminosae the lowest. All honeys were active against myoglobin-derived radicals usually formed in red meat after storage and/or heating and significant correlation (p = 0.023) was found between flavonoid content and deactivation rate of this radical. Dill &gt; almond?&gt; tangerine &gt; thistle?&gt; sulla honeys inhibite…

Cytotoxic Activity of Organotin(IV) Derivatives with Triazolopyrimidine Containing Exocyclic Oxygen Atoms

In this study cytotoxicity of organotin(IV) compounds with 1,2,4-triazolo[1,5-a]pyrimidines, Me3Sn(5tpO) (1), n-Bu3Sn(5tpO) (2), Me3Sn(mtpO) (3), n-Bu3Sn(mtpO) (4), n-Bu3Sn(HtpO2) (5), Ph3Sn(HtpO2) (6) where 5HtpO = 4,5-dihydro-5-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, HmtpO = 4,7-dihydro-5-methyl-7-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, and H2tpO2 = 4,5,6,7-tetrahydro-5,7- dioxo-[1,2,4]triazolo-[1,5-a]-pyrimidine, was assessed on three different human tumor cell lines: HCT-116 (colorectal carcinoma), HepG2 (hepatocarcinoma) and MCF-7 (breast cancer). While 1 and 3 were inactive, compounds 2, 4, 5 and 6 inhibited the growth of the three tumor cell lines with IC50 values in the submicromolar …

Partition of Indicaxanthin in Membrane Biomimetic Systems. A Kinetic and Modeling Approach

The solubilization site of indicaxanthin (Ind) in lipid bilayers was investigated by the kinetics of Ind oxidation by peroxyl radicals in water and in aqueous/L-alpha-dipalmitoyl-phosphatidylcholine (DPPC) vesicles, pH 7.4, and 37.0 and 48.0 degrees C, that is, in a gel-like and a crystal liquidlike bilayer state, respectively. The time-dependent Ind absorbance decay, matched with a successful simulation of the reaction kinetic mechanism by Gepasi software, supported a multistep pathway. Computer-assisted analysis allowed calculation of the rate constants associated with the reactions involved, the values of which decreased with increasing DPPC concentration. The binding constant calculated…

All-trans to 11-cis retinol isomerization in nuclear membrane fraction from bovine retinal pigment epithelium

Abstract Isomerization of all-trans to 11-cis retinol has been studied in a membrane preparation from the nuclear fraction of bovine retinal pigment epithelium. When the nuclear membrane preparation deprived of endogenous retinoids is incubated with 4·5 μ m all-trans-retinol, the mean value calculated for the isomerase activity is 1·32 nmol 11-cis retinol formed hr−1 mg protein−1. Simultaneous formation of all-trans and 11-cis retinyl esters is also observed in the nuclear preparation. When assayed under the same experimental condition, RPE 150 000 g post-nuclear sediment shows about 70% of the isomerase activity found in the nuclear membrane fraction. Treatment of the nuclear membrane frac…

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…

Analysis of a soluble lipid-protein complex carrying endogenous 11-cis retinaldehyde from bovine retinal pigment epithelium.

A soluble lipid-protein complex in bovine retinal pigment epithelium is shown to carry endogenous 11-cis retinaldehyde, in the extent of 15% of the total 11-cis retinaldehyde found in this tissue. The complex, analyzed with respect to its chemical composition, exhibits a lipid composition close resembling the lipid composition of the rod outer segment membrane; the SDS-PAGE evidences the presence of a number of protein bands, two of which of 34 and 27 kDa appear glycoproteins. Finally, the lipid-protein complex exhibits a discrete level of a Cathepsin D-like protease activity. From the above, the possibility is discussed that the soluble lipid-protein complex could represent some phagolysos…

Development of nucleoside phosphotransferase activity in the cerebral hemispheres of embryonal and adult chick.

In the cerebral hemispheres of the chick embryo, the level of nucleoside phosphotransferase activity is much higher than that of thymidine kinase and it increases progressively during development up to the adult stage. Therefore nucleoside phosphotransferase is not coupled with DNA synthesis.

BETANIN INHIBITS MPO-NITRITE-MEDIATED PEROXIDATION OF HUMAN LOW-DENSITY LIPOPROTEINS

Distribution of betalain pigments in red blood cells after consumption of cactus pear fruits and increased resistance of the cells to ex vivo induced oxidative hemolysis in humans.

Betalain pigments are bioavailable phytochemicals recently acknowledged as natural radical scavengers. This work, which extends previous research on the postabsorbitive fate of dietary betalains, investigated the distribution of betanin and indicaxanthin in red blood cells (RBCs) isolated from healthy volunteers (n = 8), before and during the 1-8 h interval after a cactus pear fruit meal, and the potential antioxidative activity of the pigments in these cells. A peak concentration of indicaxanthin (1.03 +/- 0.2 microM) was observed in RBCs isolated at 3 h after fruit feeding, whereas the concentration at 5 h was about half, and even smaller amounts were measured at 8 h. Indicaxanthin was no…

Quality characteristics and in vitro digestibility study of barley flour enriched ditalini pasta

A ditalini pasta with a mixture of durum wheat and beta-glucan enriched barley flour (BF) (60/40%, w/w) was found to have a final content of 5% beta-glucan (BF-ditalini). Main quality parameters of BF-ditalini, water uptake and starch-protein texture, were comparable with those of 100% durum wheat ditalini (control). After in vitro simulated intestinal digestion, the content of beta-glucan in the post intestinal (PI) supernatant of BF-ditalini processed with its cooking water (soup) was six fold higher than that of pasta asciutta. BF-ditalini soup, but not pasta asciutta, strongly delayed the hydrolysis of the starch, without difference of viscosity between PI supernatant and control. PI su…

Melatonin: Structural characterization of its non-enzymatic mono-oxygenate metabolite

Oxidation of melatonin by Fenton reagents as well as with hypochlorous acid or oxoferryl hemoglobin has been investigated. Analysis of products by low resolution/mass spectra (MS), high resolution/MS, 1H-nuclear magnetic resonance (NMR), 13C-NMR, correlated spectroscopy (COSY) and heterocorrelated spectroscopy (HETCOR) 2D NMR reveals the formation of a single mono-oxygenated product under all conditions and unequivocally assigns the N-[2-(5-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide structure, which had not been previously considered.

Synthesis, structural characterization and antitumor activity of di- and tri-organotin(IV) complexes of D-galacturonic acid

Increased eryptosis in smokers is associated with the antioxidant status and C-reactive protein levels

Abstract Cigarette smoking has been linked with oxidative stress and inflammation. In turn, eryptosis, the suicidal erythrocyte death similar to apoptosis that can be triggered by oxidative stress, has been associated with chronic inflammatory diseases including atherosclerosis. However, the link between smoking and eryptosis has not been explored so far. The aim of the present study was to determine the level of eryptotic erythrocytes in healthy male smokers (n = 21) compared to non-smokers (n = 21) and assess its relationship with systemic inflammation (CRP) as well as with antioxidant defense (GSH) and their resistance to ex-vivo induced hemolysis. Smoking caused an increase in phosphati…

Organotin(IV) derivatives with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidine and their cytotoxic activities: The importance of being conformers

Abstract The organotin(IV) compounds Me2SnCl2(dbtp)(1), Me2SnCl2(dbtp)2 (2), Et2SnCl2(dbtp) (3), Et2SnCl2(dbtp)2 (4), Et2SnCl2(dptp) (5), nBu2SnCl2(dbtp)2 (6), nBu2SnCl2(dptp) (7), Ph2SnCl2(dbtp) (8), Ph2SnCl2(EtOH)2(dptp)2 (9), where dbtp = 5,7-di-tert-butyl-1,2,4-triazolo[1,5-a]pyrimidine and dptp = 5,7-diphenyl-1,2,4-triazolo [1,5-a]pyrimidine, have been tested by MTT for their cytotoxic activity on three tumor cell lines, HepG2 (human hepatocellular carcinoma), HeLa (human cervix adenocarcinoma) and MCF-7 (human breast cancer). Except for 1 and 2, which were ineffective, all compounds significantly showed a dose-dependent anti-proliferative effect against the three cell lines. By calcul…

Absorption, excretion, and distribution of dietary antioxidant betalains in LDLs: potential health effects of betalains in humans

Background: Betalains were recently identified as natural antioxidants. However, little is known about their bioavailability from dietary sources. Objective: The objective was to evaluate the bioavailability of betalains from dietary sources. Design: The plasma kinetics and urinary excretion of betalains were studied in healthy volunteers (n 8) after a single ingestion of 500 g cactus pear fruit pulp, which provided 28 and 16 mg indicaxanthin and betanin, respectively. The incorporation of betalains in LDL and the resistance of the particles to ex vivo–induced oxidation was also researched. Results: Betanin and indicaxanthin reached their maximum plasma concentrations 3 h after the fruit me…

Absorption and distribution in erytrocytes and low density lipoproteins of betalains from cactus pear (Opuntia ficus indica) in healthy humans. Potential health effects of the dietary betalains

Antiproliferative effects of bioaccessible fractions of honeys from Sicilian black honeybee (Apis mellifera ssp. sicula) on human colorectal carcinoma cells

The aim of this study was to evaluate the antiproliferative activity of bioaccessible fractions (BFs) obtained by the internationally standardized INFOGEST static digestion method to Sicilian honeys of three distinct floral origins (Sulla, Thistle and Dill) and the Manuka honey (gold standard), and to compare their effects based on total polyphenol content (TPC). Differentiated CaCo-2 cells (intestinal-like) and non-differentiated CaCo-2 and HCT-116 colonic tumour-like cells were incubated for 24 h with BFs of honeys to test viability, apoptosis, mitochondrial membrane potential (MMP), ROS and cell cycle. TPC after digestion ranked in the following order: Dill &gt; Thistle &gt; Sulla &gt; M…

Biothiols, taurine, and lipid-soluble antioxidants in the edible pulp of Sicilian cactus pear (Opuntia ficus-indica) fruits and changes of bioactive juice components upon industrial processing.

Biothiols, taurine, and flavonols, as well as tocopherols and carotenoids have been assessed in the edible pulp of Sicilian red (Sanguigna), yellow (Surfarina), and white (Muscaredda) cultivars of cactus pear. The yellow cultivar has the highest level of reduced glutathione (GSH, 8.1 +/- 0.78 mg/100 g pulp), whereas the white cultivar showed the highest amount of cysteine (1.21 +/- 0.12 mg/100 g pulp). Taurine accounted for 11.7 +/- 1.0 mg/100 g in the yellow pulp, while lower levels were measured in the others. With the exception of kaempferol in the yellow cultivar (2.7 +/- 0.2 microg/100 g pulp), the edible pulp of cactus pear was not a source of flavonols. Very low amounts of lipid-solu…

Oxidative stress and antioxidant status in beta-thalassemia major: iron overload and depletion of lipid-soluble antioxidants

Because of continuous blood transfusions, thalassemia patients are subjected to peroxidative tissue injury by the secondary iron overload. In accordance, analysis of serum from 42 beta-thalassemia patients, aged 4 to 40 years, showed that the mean concentrations of conjugated diene lipid hydroperoxides (CD), lipoperoxides evaluated as malondialdehyde/ thiobarbituric acid (MDA/TBA) adducts, and protein carbonyls increased about twofold with respect to control. Ferritin levels were positively correlated with the amount of MDA (r = .41; P = .007) and showed a positive trend with CD (r = .31; P = .07) and protein carbonyls (r = .35; P = .054), as further evidence of the deleterious effects of h…

Antioxidant Activity of Vitamin A within Lipid Environments

New information about deleterious effects of free radicals on cell compartments, and a growing amount of associations between free radicals and various pathological conditions, have produced considerable interest in the biological defense systems against oxidative injury. The antioxidant properties of vitamin A, known for decades (Monaghan and Schmitt, 1932), have been reinvestigated in recent years in chemical as well as in biological systems. Its lipid nature and the localization within the lipophilic compartment of membranes and lipoproteins make vitamin A effective in reducing lipid peroxidation by acting as a chain-breaking antioxidant.

Indicaxanthin from Opuntia ficus-indica Crosses the Blood–Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts

Indicaxanthin is a bioactive and bioavailable betalain pigment from the Opuntia ficus-indica fruits. In this in vivo study, kinetic measurements showed that indicaxanthin is revealed in the rat brain within 1 h from oral administration of 2 μmol/ kg, an amount compatible with a dietary consumption of cactus pear fruits in humans. A peak (20 ± 2.4 ng of indicaxanthin per whole brain) was measured after 2.5 h; thereafter the molecule disappeared with first order kinetics within 4 h. The potential of indicaxanthin to affect neural activities was in vivo investigated by a microiontophoretic approach. Indicaxanthin, administered in a range between 0.085 ng and 0.34 ng per neuron, dose-dependentl…

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…

Synergistic Interactions between Vitamin A and Vitamin E against Lipid Peroxidation in Phosphatidylcholine Liposomes

Interactions between alpha-tocopherol and all-trans retinol in suppressing lipid peroxidation were studied in a unilamellar liposomal system of phosphatidylcholine from either egg or soybean, in which peroxidation was initiated by the water-soluble azo initiator 2,2-azobis(2-amidino-propane)hydrochloride and peroxidation was measured as production of conjugated diene hydroperoxides. While all-trans retinol alone was poorly effective, the combination of all-trans retinol with alpha-tocopherol caused an inhibition period far beyond the sum of the inhibition periods observed with individual antioxidants, providing evidence of synergistic interactions. Furthermore, the inhibition rate calculate…

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.…

Inhibition of the TCR-mediated activation of naïve murine T cells by Cactus Pear Fruit Extracts.

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 …

Anti-proliferative effect of main dietary phytosterols and β-cryptoxanthin alone or combined in human colon cancer Caco-2 cells through cytosolic Ca+2 – and oxidative stress induced apoptosis

β-cryptoxanthin (β-Cx) and phytosterols (Ps) have potential against different cancer types, including colon cancer. However, their combined action has not been reported so far. Human colon cancer Caco-2 cells were treated 24 h with β-Cx and/or main dietary Ps (β-sitosterol, campesterol and stigmasterol), alone or in combination, at concentrations compatible with physiological human serum levels. A decrease in cell viability due to apoptosis (rise in sub-G1 population and exposure of membrane phosphatidylserine) was accompanied with dephosphorylation of BAD, mitochondrial depolarization and caspase 3-dependent PARP cleavage, with intracellular Ca2+ influx and increase of RONS levels as initi…

Quality, functional and sensory evaluation of pasta fortified with extracts from Opuntia ficus-indica cladodes

Background The stems of Opuntia ficus-indica, known as cladodes, are a rich source of soluble fibers, which makes them an important candidate for the production of functional foods. Tagliatelle of durum wheat fortified with Opuntia cladode extract (OCE) at different levels of addition (10-30%, v/w) was prepared on a laboratory scale and quality characteristics and sensory acceptability were assessed. Results The main quality parameters (optimal cooking time, swelling index, cooking loss, dry matter) and sensory analysis on a nine-point hedonic scale were comparable with those of the control pasta sample (no added OCE) when durum wheat was supplemented with OCE at up to 20% (v/w). An in vitr…

Sintesi, caratterizzazione e attività biologica di complessi di Pt(II) con leganti eterociclici azotati e solforati e legante elilenebis(ditiocarbammato).

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

Effect on the Antioxidant, Lipoperoxyl Radical Scavenger Capacity, Nutritional, Sensory and Microbiological Traits of an Ovine Stretched Cheese Produced with Grape Pomace Powder Addition

An innovative ovine cheese enriched with red grape pomace powder (GPP) was produced to improve the functional properties of Vastedda cheese typology. Vastedda cheese making was performed adding GPP and four selected Lactococcus lactis strains (Mise36, Mise94, Mise169 and Mise190). For each strain, 40 L of pasteurized ewe’s milk was divided into two aliquots representing control and experimental trials. Control cheese (CC) production did not contain GPP, while the experimental cheese (EC) production was enriched with 1% (w/w) GPP. GPP did not slow down starter development and acid generation. Plate counts and randomly amplified polymorphic DNA (RAPD)-PCR analysis confirmed the dominance of t…

Anti-Inflammatory Effects of Nutritionally Relevant Concentrations of Oleuropein and Hydroxytyrosol on Peripheral Blood Mononuclear Cells: An Age-Related Analysis

: Immunosenescence and inflammaging facilitate the insurgence of chronic diseases. The Mediterranean diet is a non-invasive intervention to improve the chronic low-grade inflammatory status associated with aging. Olive oil oleuropein (OLE) and hydroxytyrosol (HT) demonstrated a controversial modulatory action on inflammation in vitro when tested at concentrations exceeding those detectable in human plasma. We studied the potential anti-inflammatory effects of OLE and HT at nutritionally relevant concentrations on peripheral blood mononuclear cells (PBMCs) as regards cell viability, frequency of leukocyte subsets, and cytokine release, performing an age-focused analysis on two groups of subj…

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

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

Raman Spectroscopy Technology to Monitor the Carotenoids in Skin of Thalassemia Patients: A Novel Non-Invasive Tool Relating Oxidative Stress with Iron Burden

In this work we approach the relationship between redox state and iron overload by noninvasive instrumental techniques. Intracardiac, liver iron and liver fibrosis have been monitored in transfusion-dependent thalassemia patients by magnetic resonance imaging and hepatic transient elastography examinations. These measurements have been matched with a non-invasive, and yet unexplored in clinical practice, evaluation of body’s oxidative stress through measurement of antioxidant carotenoids in skin, by a spectroscopic method based on Raman technology (RRS). The global body’s antioxidant status results from a balance between the level of antioxidants in cells and body fluids, including blood, a…

Mechanism of interaction of betanin and indicaxanthin with human myeloperoxidase and hypochlorous acid.

Hypochlorous acid (HOCl) is the most powerful oxidant produced by human neutrophils and contributes to the damage caused by these inflammatory cells. It is produced from H2O2 and chloride by the heme enzyme myeloperoxidase (MPO). Based on findings that betalains provide antioxidant and anti-inflammatory effects, we performed the present kinetic study on the interaction between the betalains, betanin and indicaxanthin, with the redox intermediates, compound I and compound II of MPO, and its major cytotoxic product HOCl. It is shown that both betalains are good peroxidase substrates for MPO and function as one-electron reductants of its redox intermediates, compound I and compound II. Compoun…

Betanin inhibits myeloperoxidase/nitrite-mediated peroxidation of low density lipoprotein.

Reducing and antioxidant properties of aqueous extracts of manna from Fraxinus ornus (Oleaceae).

Sourdough “ciabatta” bread enriched with powdered insects: Physicochemical, microbiological, and simulated intestinal digesta functional properties

Abstract Powdered mealworm (MW) and buffalo worm (BW) larvae were used to functionalize sourdough Italian-style breads. Sourdough inoculum was started with Levilactobacillus brevis, Weissella cibaria and Leuconostoc citreum. The doughs were SBS (semolina plus powdered BW larvae and sourdough) and SMS (semolina plus powdered MW larvae and sourdough) whose pHs (4.32 and 4.21, respectively) were higher than that of control (3.81). The highest fermentation quotient (lactate/acetate molar ratio) was recorded in SMS (4.46). LAB reached viable counts of about 109 CFU g−1 in almost all doughs. Insects impacted bread VOCs with dodecanal, 2.4-dodecadienal and 2-octenal-2-butyl. SBS and SMS increased …

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…

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…

Antioxidant reactions of all-trans retinol in phospholipid bilayers: effect of oxygen partial pressure, radical fluxes, and retinol concentration.

Lipoperoxyl radical-scavenging activity of retinol in unilamellar soybean phosphatidylcholine liposomes was studied under a variety of conditions to appreciate to what extend retinol may be considered an effective antioxidant. Peroxidation, initiated by 2 mM 2,2'-azobis(amidino-propane)hydrochloride (AAPH), was carried out at 160 torr O2 or at 15 torr O2, in the absence or in the presence of 10 to 40 mM retinol. As evaluated by the length of the inhibition periods, t(inh), and by the ratio between the inhibition and propagation rate, R(inh)/R(p), the antioxidant activity of retinol was higher at 15 torr O2 than at 160 torr O2. The consumption rate of retinol was markedly faster at 160 torr …

Cactus pear fruit extract exerts anti-inflammatory effects in carrageenin-induced rat pleurisy

Nutritional research has recently shifted from alleviating nutrient deficiencies to chronic disease prevention. In this study activity of cactus pear fruit extract (CPFE) from Opuntia ficus-indica (L.) Mill. has been investigated in carrageenin-induced pleurisy, a rat model of acute inflammation. In our experimental design rat pleurisy was achieved by the injection of 0.2 ml of λ-carrageenin in the pleural cavity. At selected time points, rats were sacrificed; cells recruited in pleura were counted and exudates collected to analyse inflammatory parameters such as NO, PGE2, IL-1β, TNF-α. CPFE (in the range between 5 and 20 g fresh fruit equivalent/kg), orally given 30 min before the injectio…

Reuse of almond by-products: Functionalization of traditional semolina sourdough bread with almond skin

Almond production generates large amounts of by-products rich in polyphenols. In this study, almond skin was explored as a valuable food ingredient in bread making. To this purpose, almond skin was used to produce functional products modifying a traditional sourdough bread recipe. The doughs were prepared replacing semolina with powdered almond skin (PAS) at 5 and 10 % (w/w). Sourdough inoculum was started with a mix of lactic acid bacteria (LAB) and propagated in semolina until reaching pH 3.7. The pH of PAS added breads was higher than that of control (CTR) breads before and after fermentation. Plate counts showed a similar evolution of LAB and total mesophilic microorganisms, but members…

Health benefits and bioactive components of the fruits from Opuntia ficus indica [L] Mill

Reaction of melatonin with hemoglobin-derived oxoferryl radicals and inhibition of the hydroperoxide-induced hemoglobin denaturation in red blood cells

Melatonin has been shown to act as a radical scavenger in various chemical and biological model systems in vitro. Kinetic evidence is now provided showing that melatonin inhibits the irreversible degradation of hemoglobin (Hb), when incubated with red blood cells exposed to the oxidant activity of cumene hydroperoxide (cumOOH). A decrease of heme loss and accumulation of soluble methemoglobin (met-Hb) are explained in terms of the interaction of the indoleamine with perferryl Hb ( . Hb[Fe IV = O]), a highly reactive Hb-derived radical species responsible for the irreversible Hb degradation. A kinetic study, in pure chemical solution, showed that melatonin can effectively reduce the oxoferry…

Inhibitory effects of indicaxanthin on mouse ileal contractility: analysis of the mechanism of action.

Recently, we have showed that indicaxanthin, the yellow betalain pigment abundant in the fruit of Opuntia ficus indica, has remarkable spasmolytic effects on the intestinal contractility in vitro. Thus, the purpose of the present study was to investigate the mechanism of action underlying the observed response. We used organ bath technique to record the mechanical activity of the mouse ileum longitudinal muscle and ELISA to measure the levels of cAMP. Indicaxanthin induced inhibitory effects on spontaneous mechanical activity, which were unaffected by indomethacin, a non-selective inhibitor of cycloxygenase; 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a selective inhibitor of nitric oxide-…

Indicaxanthin, a multi-target natural compound from Opuntia ficus-indica fruit: From its poly-pharmacological effects to biochemical mechanisms and molecular modelling studies

Abstract Over the latest years phytochemical consumption has been associated to a decreased risk of both the onset and the development of a number of pathological conditions. In this context indicaxanthin, a betalain pigment from Opuntia ficus-indica fruit, has been the object of sound research. Explored, at first, for its mere antioxidant potential, Indicaxanthin is now regarded as a redox-active compound able to exert significant poly-pharmacological effects against several targets in a number of experimental conditions both in vivo and in vitro. This paper aims to provide an overview on the therapeutical effects of indicaxanthin, ranging from the anti-inflammatory to the neuro-modulatory…

A novel compound of triphenyltin(IV) with N-tert-butoxycarbonyl-L-ornithine causes cancer cell death by inducing a p53-dependent activation of the mitochondrial pathway of apoptosis

The triphenyltin(IV) compound with N-tert-butoxycarbonyl-L-ornithine (Boc-Orn-OH), [Ph3Sn(Boc-Orn-O)], was synthesized and characterized by elemental analysis, FT-IR, solution1H,13C and119Sn NMR and ESI mass spectrometry. The organotin(IV) compound inhibited at very low micromolar concentrations the growth of human tumor cell lines HepG2 (hepatocarcinoma cells), MCF-7 (mammary cancer) and HCT116 (colorectal carcinoma) while it did not affect the viability of non-malignant human-derived hepatic cells Chang. The mechanism of the antiproliferative effect of Ph3Sn(Boc-Orn-O), investigated on human hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of plasma membrane …

Modulation of Human Motor Cortical Excitability and Plasticity by Opuntia Ficus Indica Fruit Consumption: Evidence from a Preliminary Study through Non-Invasive Brain Stimulation

Indicaxanthin (IX) from Opuntia Ficus Indica (OFI) has been shown to exert numerous biological effects both in vitro and in vivo, such as antioxidant, anti-inflammatory, neuro-modulatory activity in rodent models. Our goal was to investigate the eventual neuro-active role of orally assumed fruits containing high levels of IX at nutritionally-relevant amounts in healthy subjects, exploring cortical excitability and plasticity in the human motor cortex (M1). To this purpose, we applied paired-pulse transcranial magnetic stimulation and anodal transcranial direct current stimulation (a-tDCS) in basal conditions and followed the consumption of yellow cactus pear fruits containing IX or white ca…

Attività anti-proliferativa di derivati di organostagno(IV) con Na-Boc-Ornitina e studio dell’azione pro-apoptotica del derivato Ph3Sn(Boc- Orn)

Nuovi composti di organostagno(IV) [R3SnL e R¢2SnL2 (R = Me, Ph e R¢= Me, nBu, HL= Na-Boc-Ornitina)] sono stati sintetizzati e caratterizzati sia allo stato solido (FT-IR) che in soluzione (1H e 13C NMR) per poterne valutare la citotossicità in linee cellulari tumorali [1]. Na-Boc-Ornitina si comporta come un legante chelante dello stagno con il gruppo carbossilato, mentre il gruppo amminico Na-protetto è esente dalla coordinazione. I composti sono stati testati per l’attività citotossica in vitro su cellule neoplastiche umane HepG2 di epatocarcinoma ed MCF7 di cancro al seno. L’effetto dei composti, nel range da 0.5 a 25 μM, dopo 24 h di incubazione è stato valutato mediante saggio MTT. Il…

The purification and properties of nucleoside phosphotransferase from mucosa of chicken intestine

Abstract (1) Nucleoside phosphotransferase (nucleotide:3′-deoxynucleoside 5′-phosphotransferase, EC 2.7.1.77) has been purified from chicken intestine mucosa to apparent homogeneity. The enzyme is represented by a multisubunit protein at different degrees of association. It can dissociate into a compoenent with a marked fall in catalytic activity. (2) The associated forms are similar to the enzyme previously purified from chick embryo as regards: substrate specificity both with respect to nucleoside monophosphate donors and to deoxyribonucleoside acceptors; sigmoidicity in the rate curve with a variable phosphate donor; instability to heat, dilution and lowering of pH; the activating and pr…

Indicaxanthin Dietetics: Past, Present, and Future

The betalamic acid derivatives of betalain pigments (purple-red betacyanins and yellow betaxanthins) are dietary compounds occurring in a few plant foods including beets (Beta vulgaris) and cactus pears (Opuntia spp.). Belonging to betaxanthins, indicaxanthin is rich in yellow cactus pear (Opuntia ficus indica L., Mill). High dietary bioavailability of indicaxanthin in humans, as well as its physicochemical properties, radical-scavenging and antioxidant activities in various experimental models suggest this molecule as a promising nutraceutical agent and open perspectives for its applications. Life-long modulatory activity at the epigenetic level now appears as the new frontier to shed ligh…

Mechanism of Reaction of Melatonin with Human Myeloperoxidase

Recently, it was suggested that melatonin (N-acetyl-5-methoxytryptamine) is oxidized by activated neutrophils in a reaction most probably involving myeloperoxidase (Biochem. Biophys. Res. Commun. (2000) 279, 657-662). Myeloperoxidase (MPO) is the most abundant protein of neutrophils and is involved in killing invading pathogens. To clarify if melatonin is a substrate of MPO, we investigated the oxidation of melatonin by its redox intermediates compounds I and II using transient-state spectral and kinetic measurements at 25 degrees C. Spectral and kinetic analysis revealed that both compound I and compound II oxidize melatonin via one-electron processes. The second-order rate constant measur…

Indicaxanthin exerts anti-inflammatory effects on carrageenin-induced rat pleurisy.

Synthesis, properties, antitumor and antibacterial activity of new Pt(II) and Pd(II) complexes with 2,2′-dithiobis(benzothiazole) ligand

Mono- and binuclear Pt(II) and Pd(II) complexes with 2,20-dithiobis(benzothiazole) (DTBTA) ligand are reported. [Pt(DTBTA)(DMSO)Cl]Cl∙CHCl3 (1) and [Pd2(m-Cl)2(DTBTA)2]Cl2 (2) have been synthesized and structurally characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy, MS spectrometry and the content of platinum and palladium was determined using a flame atomic spectrometer. Two different coordination modes of 1 and 2 complexes were found; in both complexes, the coordination of Pt(II) and Pd(II) ions involves the N(3) atoms of the ligand but the binuclear complex 2, is a cis-chloro-bridged palladium complex. Evaluation of their in vitro antitumor activity against two human tu…

Contribution of vitamin A to the oxidation resistance of human low density lipoproteins.

This study investigated the antioxidant contribution of vitamin A in protecting human low density lipoprotein (LDL) against copper-stimulated oxidation. The presence of small amounts of retinol (0.033 ± 0.012 nmol/mol LDL) and retinyl palmitate (0.036 ± 0.021 nmol/mol LDL) was routinely ascertained in the LDL. A single oral supplementation with 20,000 IU vitamin A caused a two- to three-fold increase of retinol and retinyl palmitate in the LDL isolated 8 h after the supplementation. In comparison to autologous-control LDL, vitamin A-enriched LDL were more resistant to oxidation, as expressed both by a clear delay in the onset of lipid peroxidation and by a reduction of the rate of conjugate…

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 …

Oxidation of melatonin by oxoferryl hemoglobin: A mechanistic study

Reaction of melatonin with the hypervalent iron centre of oxoferryl hemoglobin, produced in aqueous solution from methemoglobin and H2O2, has been investigated at 37 degrees C and pH 7.4, by absorption spectroscopy. The reaction results in reduction of the oxoferryl moiety with formation of a heme-ferric containing hemoprotein. Stopped-flow spectrophotometric measurements provide evidence that the reduction of oxoferryl-Hb by melatonin is first-order in oxoferryl-Hb and first-order in melatonin. The bimolecular reaction constant at pH 7.4 and 37 degrees C is 112 +/- 1.0 M(-1) s(-1). Two major oxidation products from melatonin have been found by gas chromatography-mass spectroscopy: the cycl…

Cigarette Smoke Extract Induces p38 MAPK-Initiated, Fas-Mediated Eryptosis

Eryptosis is a physiological mechanism for the clearance of senescent or damaged erythrocytes by phagocytes. Excessive eryptosis is stimulated under several pathologies and associated with endothelial injury and thrombosis. Cigarette smoke (CS) is an established risk factor for vascular diseases and cigarette smokers have high-levels of eryptotic erythrocytes. This study, for the first time, investigates the mechanism by which CS damages red blood cells (RBCs). CS extract (CSE) from commercial cigarettes was prepared and standardized for nicotine content. Cytofluorimetric analysis demonstrated that treatment of human RBCs with CSE caused dose-dependent, phosphatidylserine externalization an…

Anti-Proliferative Activity of A Hydrophilic Extract of Manna from Fraxinus angustifolia Vahl through Mitochondrial Pathway-Mediated Apoptosis and Cell Cycle Arrest in Human Colon Cancer Cells

Manna is produced from the spontaneous solidification of the sap of some Fraxinus species, and, owing its content in mannitol, is used in medicine as a mild laxative. Manna is also a rich source of characteristic bio-phenols with reducing, antioxidant and anti-inflammatory properties. This study assesses the activity of a hydrophilic extract of manna (HME) on cellular and molecular events in human colon-rectal cancer cells. HME showed a time- and concentration-dependent anti-proliferative activity, measured by MTT assay, in all the cell lines examined, namely Caco-2, HCT-116 and HT-29. The amounts of HME that caused 50% of cell death after a 24 h treatment were 8.51 &plusmn

Indicaxanthin from cactus pear fruit exerts anti-inflammatory effects in carrageenin-induced rat pleurisy.

Nutritional research has shifted recently from alleviating nutrient deficiencies to chronic disease prevention. We investigated the activity of indicaxanthin, a bioavailable phytochemical of the betalain class from the edible fruit of Opuntia ficus-indica (L. Miller) in a rat model of acute inflammation. Rat pleurisy was achieved by injection of 0.2 mL of l-carrageenin in the pleural cavity, and rats were killed 4, 24, and 48 h later; exudates were collected to analyze inflammatory parameters, such as nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1b (IL-1b), and tumor necrosis factor-a (TNF-a); cells recruited in pleura were analyzed for cyclooxygenase-2 (COX-2), inducible nitric …

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…

Haemolymphatic Parameters in Two Aquaculture Crustacean Species Cherax destructor (Clark, 1836) and Cherax quadricarinatus (Von Martens, 1868)

In the last few years, there has been a notable development in the breeding of freshwater shrimp (astaciculture), which involved various species and in particular, the two Australian Parastacidae species, Cherax destructor and Cherax quadricarinatus. Information about the haemolymphatic parameters of these two species is fragmentary, and filling these gaps becomes important given their importance in aquaculture. Cellular and biochemical parameters were analyzed in both species to create a reference baseline for these parameters to identify the state of welfare or suffering of these animals. The results showed that the total haemocyte count, haemocyte subpopulations, enzymatic activities and…

Haemolymphatic parameters in two aquaculture crustacean species Cherax destructor (Clark, 1836) and Cherax quadricarinatus (von Martens, 1868)

The growing demand for animal proteins of aquatic origin such as fish, molluscs and crustaceans have prompted some European and Italian companies to focus their attention on some species of freshwater crustaceans such as Cherax destructor and Cherax quadricarinatus. They are among the largest freshwater decapods, matures early, females can lay over a thousand eggs in a single brood and has a broad environmental tolerance. All these characteristics make it highly appreciated species for aquaculture and few years ago their breeding has spread to Europe and recently also in Italy (Sicily). Although some commercial yabby farms have been studied these species from different points of view (dieta…

ADHESION OF ACTIVATED HL-60 TO ENDOTHELIAL CELLS UP-REGULATES ICAM-1 EXPRESSION.

Nucleoside phosphotransferase in animal tissues. Tissue distribution and kinetic properties

Amphibian, avian and mammal tissues contain a nucleoside phosphotransferase clearly different from those previously described in vegetables and bacteria. Whatever the animal source, the enzyme showed many similar characteristics as far as substrate specificity, dependence upon Mg2+, instability at 37 degrees C, and the protecting effect of nucleotides were concerned. Moreover, when submitted to gel filtration, the enzyme behaved in all cases as a dissociable high molecular weight protein, whose degree of association was controlled by nucleotides. In amphibian and avian tissues multiple forms of the enzyme seem to be present which differ for the substrate concentration at half-maximal veloci…

Suicidal Erythrocyte Death in Metabolic Syndrome.

Eryptosis is a coordinated, programmed cell death culminating with the disposal of cells without disruption of the cell membrane and the release of endocellular oxidative and pro-inflammatory milieu. While providing a convenient form of death for erythrocytes, dysregulated eryptosis may result in a series of detrimental and harmful pathological consequences highly related to the endothelial dysfunction (ED). Metabolic syndrome (MetS) is described as a cluster of cardiometabolic factors (hyperglycemia, dyslipidemia, hypertension and obesity) that increases the risk of cardiovascular complications such as those related to diabetes and atherosclerosis. In the light of the crucial role exerted …

Lipoperoxyl Radical Scavenging and Antioxidative Effects of Red Beet Pigments

Aerobic life is characterized by a steady formation of reactive oxygen species and free radicals, which is almost entirely counteracted by endogenous primary and secondary antioxidant systems. Maintenance of these systems is then imperative to ensure a continuous defense to cells and to avoid conditions known as oxidative stress. Apart from antioxidant vitamins, many compounds from the plant kingdom are now considered very helpful to maintain a proper cell redox balance. Among them, betalain pigments have received recent attention. Betanin (betanidin-5-O-β glucoside) is the main betacyanin from red beet. Redox potential, ability to interact with lipid structures and bioavailability in human…

Absorption and distribution in erythrocytes and low density lipoproteins of betalains from cacus pear (Opuntia Ficus Indica) in healthy humans. Potential health effects of the dietary betalains

ABSTRACT Background: Betalains were recently identified as natural antioxidants. However, little is known about their bioavailability from dietary sources. Objective: The objective was to evaluate the bioavailability of betalains from dietary sources. Design: The plasma kinetics and urinary excretion of betalains were studied in healthy volunteers (n = 8) after a single ingestion of 500 g cactus pear fruit pulp, which provided 28 and 16 mg indicaxanthin and betanin, respectively. The incorporation of betalains in LDL and the resistance of the particles to ex vivo-induced oxidation was also researched. Results: Betanin and indicaxanthin reached their maximum plasma concentrations 3 h after t…

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…

Dietary phytochemicals in the protection against oxysterol-induced damage.

The intake of fruits and vegetables is associated with reduced incidence of many chronic diseases. These foods contain phytochemicals that often possess antioxidant and free radical scavenging capacity and show anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative disorders. Many factors can be included in the etiopathogenesis of all of these multifactorial diseases that involve oxidative stress, inflammation and/or cell death processes, oxysterols, i.e. cholesterol oxidation products (COPs) as well as phytosterol oxidat…

Anti-Eryptotic Activity of Food-Derived Phytochemicals and Natural Compounds

Human red blood cells (RBCs), senescent or damaged due to particular stress, can be removed by programmed suicidal death, a process called eryptosis. There are various molecular mechanisms underlying eryptosis. The most frequent is the increase in the cytoplasmic concentration of Ca2+ ions, later exposure of erythrocytes to oxidative stress, hyperosmotic shock, ceramide formation, stimulation of caspases, and energy depletion. Phosphatidylserine (PS) exposed by eryptotic RBCs due to interaction with endothelial CXC-Motiv-Chemokin-16/Scavenger-receptor, causes the RBCs to adhere to vascular wall with consequent damage to the microcirculation. Eryptosis can be triggered by various xenobiotics…

Antioxidant activity in solution and biological membranes of seven cultivars of Sicilian peach (Prunus Persica, L. Mill).

In vitro digestion of beta glucan enriched pasta and antioxidant potential of digesta

New Tripentone Analogs with Antiproliferative Activity

Tripentones represent an interesting class of compounds due to their significant cytotoxicity against different human tumor cells in the submicro-nanomolar range. New tripentone analogs, in which a pyridine moiety replaces the thiophene ring originating the fused azaindole system endowed with anticancer activity viz 8H-thieno[2,3-b]pyrrolizinones, were efficiently synthesized in four steps with fair overall yields (34–57%). All tripentone derivatives were tested in the range of 0.1–100 μM for cytotoxicity against two human tumor cell lines, HCT-116 (human colorectal carcinoma) and MCF-7 (human breast cancer). The most active derivative, with GI50 values of 4.25 µM and 20.73 µM for HCT-116 a…

The Use of Winery by-Products to Enhance the Functional Aspects of the Fresh Ovine “Primosale” Cheese

Fresh ovine “primosale” cheese was processed with the addition of grape pomace powder (GPP). Cheese making was performed using pasteurized ewes’ milk and four selected Lactococcus lactis strains (Mise36, Mise94, Mise169 and Mise190) inoculated individually. For each strain the control cheese (CCP) was not added with GPP, while the experimental cheese (ECP) was enriched with 1% (w/w) GPP. GPP did not influence the starter development that reached levels of 109 CFU/g in all final cheeses. The comparison of the bacterial isolates by randomly amplified polymorphic DNA (RAPD)-PCR showed the dominance of the added strains over indigenous milk bacteria resistant to pasteurization. GPP addition red…

The inhibitory effect of D-glucosamine on thymidine kinase in chick embryo retinas and HeLa cells

D-Glucosamine markedly inhibits thymidine incorporation into the TCA-insoluble fraction and thymidine kinase activity in HeLa cells. Both the inhibitory effects are also observed in isolated retinas of chick embryos. In this case the inhibitory effects are age-dependent and the magnitude of the responses decreases with embryonic development. In addition the time of exposure to D-glucosamine which is necessary to reveal the inhibitory effect on thymidine kinase increases with the age of the embryos.

Reaction of melatonin with lipoperoxyl radicals in phospholipid bilayers.

Melatonin, at 5 to 500 microM was incorporated in unilamellar soybean phosphatidylcholine (PC) liposomes, the peroxidation of which was induced by 2,2'-azobis (2-amidinopropane-hydrochloride) (AAPH), and measured as production of conjugated diene lipid hydroperoxides. Concentration as low as 5 and 10 microM were poorly effective in reducing lipid peroxidation. Melatonin at 30 to 500 microM caused short inhibition periods, increasing with, but not linearly related to concentration, with a concurrent net decrease of the propagation rate. The time course of melatonin oxidation, measured as loss of fluorescence, was studied during the AAPH-stimulated peroxidation of soybean PC liposomes, or whe…

Fruit and Vegetable Derived Waste as a Sustainable Alternative Source of Nutraceutical Compounds

Dietary phytochemicals are widely investigated in the eld of chemistry, biology, nutrition, and medicine for their potential health-promoting e‚ects. Indeed, many in vitro and in vivo studies provide evidence that a number of these compounds are involved in the prevention and/or control of chronic disorders such as cancer and cardiovascular diseases. e exponential growth of plant waste production from the agrofood industry is a critical global issue, considering its storage, disposal, environmental impact, and potential health risks. However, the exploitation of plant wastes/by-products for the recovery of added-value compounds o‚ers new avenue for industrial growth and waste management. I…

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

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

Synthesis of platinum complexes with 2-(5-perfluoroalkyl-1,2,4-oxadiazol-3yl)-pyridine and 2-(3-perfluoroalkyl-1-methyl-1,2,4-triazole-5yl)-pyridine ligands and their in vitro antitumor activity.

Five new mononuclear Pt(II) complexes with 5-perfluoroalkyl-1,2,4-oxadiazolyl-pyridine and 3-perfluoroalkyl-1,2,4-triazolyl-pyridine ligands are reported. The ligands 2-(5-perfluoroheptyl-1,2,4-oxadiazole-3yl)-pyridine (pfhop), 2-(5-perfluoropropyl)-1,2,4-oxadiazole-3yl)-pyridine (pfpop), 2-(3-perfluoroheptyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfhtp), 2-(3-perfluoropropyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfptp) and their complexes [PtCl2(pfhop)(2)]center dot 1.5 DMSO (2a), [PtCl2(pfpop)(2)]center dot 1.5 DMSO (3a), [PtCl2(pfhtp)(2)]center dot 1.5 DMSO (4a), PtCl2(pfhtp) (4b), [PtCl2(PfPtP)(2)]center dot 1.5 DMSO (5a) have been synthesized and structurally characterized. The comple…

Synthesis of 5H-pyrido[3,2-b]pyrrolizin-5-one tripentone analogs with antitumor activity

Abstract Pyrrolizinones represent an interesting class of compounds with varied degrees of structural complexity and pharmacological activity. Among these, 9H-pyrido[2,3-b]pyrrolizin-9-one, tripentone analogs, recently reported by us, showed significant antiproliferative activity against human tumor cell lines, inducing apoptosis and not affecting viability of Caco-2 differentiated in normal intestinal-like cells. Considering their interesting biological activity, their 5H-pyrido[3,2-b]pyrrolizin-5-one analogs were efficiently synthesized in good to excellent yields (61–91%). All tripentone derivatives were tested to assess their cytotoxicity against two human tumor cell lines, HCT-116 (hum…

3-[4-(1H-indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, nortopsentin Analogues with antiproliferative activity

A new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and the indole unit bound to position 2 of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently synthesized. Two of the new nortopsentin analogues showed good antiproliferative effect against the totality of the NCI full panel of human tumor cell lines (~60) having GI50 values ranging from low micromolar to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, investigated on human hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and mitochondrial dysfunctio…

SINTESI E ATTIVITÀ PROAPOPTOTICA SU LINEE CELLULARI TUMORALI UMANE DI COMPLESSI DI Pt (II) CON LEGANTI AZOLICI FLUORURATI

Effects of extract from Opuntia Ficus Indica Fruits on mouse ileal motility in vitro.

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…

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…

CCDC 1908619: Experimental Crystal Structure Determination

Related Article: Alessandro Attanzio, Simone D’Agostino, Rosalia Busà, Anna Frazzitta, Simona Rubino, Maria Assunta Girasolo, Piera Sabatino, Luisa Tesoriere|2020|Molecules|25|859|doi:10.3390/molecules25040859

CCDC 997203: Experimental Crystal Structure Determination

Related Article: Maria Assunta Girasolo, Alessandro Attanzio, Piera Sabatino, Luisa Tesoriere, Simona Rubino, Giancarlo Stocco|2014|Inorg.Chim.Acta|423b|168|doi:10.1016/j.ica.2014.07.015

CCDC 1908620: Experimental Crystal Structure Determination

Related Article: Alessandro Attanzio, Simone D’Agostino, Rosalia Busà, Anna Frazzitta, Simona Rubino, Maria Assunta Girasolo, Piera Sabatino, Luisa Tesoriere|2020|Molecules|25|859|doi:10.3390/molecules25040859