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

Il fitochimico indicaxantina previene stress ossidativo, arresto del ciclo cellulare ed apoptosi indotta da 7-Ketocolesterolo in monociti-macrofagi umani in coltura.

PHYTOCHEMICAL INDICAXANTHIN PREVENTS 7-ketoCHOLESTEROL-INDUCED OXIDATIVE STRESS, CELL CYCLE ARREST AND APOPTOSIS IN HUMAN MONOCYTES- MACROPHAGES.

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…

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…

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…

Protective, antioxidant and antiproliferative activity of grapefruit integropectin on sh-sy5y cells

Tested in vitro on SH-SY5Y neuroblastoma cells, grapefruit IntegroPectin is a powerful protective, antioxidant and antiproliferative agent. The strong antioxidant properties of this new citrus pectin, and its ability to preserve mitochondrial membrane potential and morphology, severely impaired in neurodegenerative disorders, make it an attractive therapeutic and preventive agent for the treatment of oxidative stress-associated brain disorders. Similarly, the ability of this pectic polymer rich in RG-I regions, as well as in naringin, linalool, linalool oxide and limonene adsorbed at the outer surface, to inhibit cell proliferation or even kill, at high doses, neoplastic cells may have open…

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, 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…

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…

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…

Fruit Juices: Technology, Chemistry, and Nutrition 2.0

In recent years, the food industry has increased its interest in the development of functional foods, including fruit juices, due to the increased demand among consumers for foods and beverages that benefit and improve our health [...]

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…

New Therapeutic Approaches against Inflammation and Oxidative Stress in Neurodegeneration

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…

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…

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

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…

In vitro digestion of beta glucan enriched pasta: polysaccharide molecular characterization and antioxidant activity of bioaccessible fraction.

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.

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…

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…

Proteostasis Deregulation in Neurodegeneration and Its Link with Stress Granules: Focus on the Scaffold and Ribosomal Protein RACK1.

The role of protein misfolding, deposition, and clearance has been the dominant topic in the last decades of investigation in the field of neurodegeneration. The impairment of protein synthesis, along with RNA metabolism and RNA granules, however, are significantly emerging as novel potential targets for the comprehension of the molecular events leading to neuronal deficits. Indeed, defects in ribosome activity, ribosome stalling, and PQC—all ribosome-related processes required for proteostasis regulation—can contribute to triggering stress conditions and promoting the formation of stress granules (SGs) that could evolve in the formation of pathological granules, usually occurring during ne…

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…

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…

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 …

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

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 > almond?> tangerine > thistle?> 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 …

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…

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…

CHEMICAL CHARACTERIZATION AND BIOLOGICAL PROPERTIES OF MACROALGAE EXTRACTS

Marine species are a rich source of bioactive molecules and among them, it is known that marine algae produce different secondary metabolites for which different biological activities such as: immunomodulatory (Raposo et al., 2016), antioxidant (Fisch et al., 2003) and antimicrobial (Pinteus et al., 2015) were demostrated. The aim of this study was chemical charac- terize the extracts of three macroalgae species: Carpodesmia crinite (Duby, Orellana & Sansón, 2019), Carpodesmia brachy- carpa (J. Agardh, Orellana & Sansón 2019, WoRMS, 2023), Ericaria brachycarpa (J. Agardh, Molinari & Guiry, 2020), Asparagopsis taxiformis (Delile) Trevisan 1845) to evaluate also their biological a…

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 > Thistle > Sulla > M…

Composizione chimica dell'olio essenziale di Ptilostemon greuteri (Compositae)

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…

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.…

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).

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…

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…

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…

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…

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…

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…

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

Neuroprotective, antioxidant and antiproliferative activity of grapefruit IntegroPectin on SH-SY5Y cells

AbstractTested in vitro on SH-SY5Y neuroblastoma cells, grapefruit IntegroPectin is a powerful neuroprotective, antioxidant and antiproliferative agent. The strong antioxidant properties of grapefruit IntegroPectin, and its ability to preserve mitochondrial membrane potential and morphology, severely impaired in neurodegenerative disorders, make this new biopolymer highly soluble in water an attractive therapeutic agent for oxidative stress-associated brain disorders. Similarly, the ability of this new citrus pectin rich in naringin, linalool, linalool oxide and limonene adsorbed at the outer surface to inhibit cell proliferation or even kill, at high doses, neoplastic cells, coupled to its…

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…

Cellular Senescence in Age-Related Diseases: Molecular Bases and Therapeutic Interventions

Due to the increase in life expectancy, the aging population around the globe has been growing significantly and is estimated to triple by 2050 [...]

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…

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 …

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…

BROILER CHICKENS AND THEIR HEALTH STATUS IN FARM: WINE WASTE, AN ADDED VALUE ON FEEDING

Various key economic sectors of the National and Sicilian economy, in addition to contributing to the economic growth also cause a considerable production of waste which today are a problem both for companies then for the environment. For this reason, there is considerable interest in this waste and in the possibility of their reuse to extract bioactive molecules with added value, all in accordance with the objectives of the Blue Economy. In this regard, it has already been demonstrated that from the production waste of various economic sectors it is possible to obtain bioactive molecules with anticancer, antimicrobial, cosmetic, antioxidant and nutraceutical properties (Mauro et al., 2022)…

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…

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…

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…

CAMPTOTHECIN INDUCES S-PHASE ARREST AND APOPTOSIS IN MG63 OSTEOSARCOMA CELLS.

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

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…

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