Determination of Commercial Animal and Vegetable Milks’ Lipid Profile and Its Correlation with Cell Viability and Antioxidant Activity on Human Intestinal Caco-2 Cells

none9openantonella aresta; Stefania De Santis; Alessia Carocci; Alexia Barbarossa; Andrea Ragusa; Nicoletta De Vietro; Maria Lisa Clodoveo; Filomena Corbo; Carlo ZAMBONINAresta, Antonella; De Santis, Stefania; Carocci, Alessia; Barbarossa, Alexia; Ragusa, Andrea; De Vietro, Nicoletta; Lisa Clodoveo, Maria; Corbo, Filomena; Zambonin, Carl

Pomegranate: Nutraceutical with Promising Benefits on Human Health

Pomegranate is an old plant made up by flowers, roots, fruits and leaves, native to Central Asia and principally cultivated in the Mediterranean and California (although now widespread almost all over the globe). The current use of this precious plant regards not only the exteriority of the fruit (employed also for ornamental purpose) but especially the nutritional and, still potential, health benefits that come out from the various parts composing this one (carpellary membranes, arils, seeds and bark). Indeed, the phytochemical composition of the fruit abounds in compounds (flavonoids, ellagitannins, proanthocyanidins, mineral salts, vitamins, lipids, organic acids) presenting a significant biological and nutraceutical value. For these reasons, pomegranate interest is increased over the years as the object of study for many research groups, particularly in the pharmaceutical sector. Specifically, in-depth studies of its biological and functional properties and the research of new formulations could be applied to a wide spectrum of diseases including neoplastic, cardiovascular, viral, inflammatory, metabolic, microbial, intestinal, reproductive and skin diseases. In this review, considering the increasing scientific and commercial interest of nutraceuticals, we reported an update of the investigations concerning the health-promoting properties of pomegranate and its bioactive compounds against principal human pathologies

Synthesis, anticancer and antioxidant properties of new indole and pyranoindole derivatives

The indole scaffold has been recognized, over the years, as a model for the synthesis of compounds with anticancer activity by dint of its substantiated ability to act via multiple mechanisms, which also involves the inhibition of enzymes engaged in DNA replication. In this regard, a new series of indole and pyranoindole derivatives have been prepared, some of which showed good antitumor activity and proved their inhibitory effects on the tubulin target. The anticancer activity of the newly synthesized compounds has been evaluated on breast cancer cell lines, as MCF-7 and MDA-MB231, cervical cancer cells line HeLa and Ishikawa endometrial cancer cell line. Among the compounds under study, 7 exhibited a good antitumor activity on HeLa cell line (IC50 = 3.6 ± 0.5), leading to cell death by apoptosis due to the inhibition of tubulin polymerization, which demonstrated that the compound can explicate its function in a similar way to Vinblastine, a well-known inhibitor of tubulin polymerization. The data were also confirmed by in silico assays. No cytotoxicity against normal cells has been detected. Furthermore, in order to investigate the antioxidant properties, DPPH and ABTS tests were performed, together with fluorescence assays on 3T3-L1 cells. All our findings taken together led us to consider compound 7 a favourable candidate for the battle against cancer

Synthesis, computational and experimental pharmacological studies for (thio)ether-triazine 5-HT6R ligands with noticeable action on AChE/BChE and chalcogen-dependent intrinsic activity in search for new class of drugs against Alzheimer's disease

Alzheimer's disease is becoming a growing problem increasing at a tremendous rate. Serotonin 5-HT6 receptors appear to be a particularly attractive target from a therapeutic perspective, due to their involvement not only in cognitive processes, but also in depression and psychosis. In this work, we present the synthesis and broad biological characterization of a new series of 18 compounds with a unique 1,3,5-triazine backbone, as potent 5-HT6 receptor ligands. The main aim of this research is to compare the biological activity of the newly synthesized sulfur derivatives with their oxygen analogues and their N-demethylated O- and S-metabolites obtained for the first time. Most of the new triazines displayed high affinity (Ki < 200 nM) and selectivity towards 5-HT6R, with respect to 5-HT2AR, 5-HT7R, and D2R, in the radioligand binding assays. For selected, active compounds crystallographic studies, functional bioassays, and ADME-Tox profile in vitro were performed. The exciting novelty is that the sulfur derivatives exhibit an agonistic mode of action contrary to all other compounds obtained to date in this chemical class herein and previously reported. Advanced computational studies indicated that this intriguing functional shift might be caused by presence of chalcogen bonds formed only by the sulfur atom. In addition, the N-demethylated derivatives have emerged highly potent antioxidants and, moreover, show a significant improvement in metabolic stability compared to the parent structures. The cholinesterase study present micromolar inhibitory AChE and BChE activity for both 5-HT6 agonist 19 and potent antagonist 5. Finally, the behavioral experiments of compound 19 demonstrated its antidepressant-like properties and slight ability to improve cognitive deficits, without inducing memory impairments by itself. Described pharmacological properties of both compounds (5 and 19) allow to give a design clue for the development of multitarget compounds with 5-HT6 (both agonist and antagonist)/AChE and/or BChE mechanism in the group of 1,3,5-triazine derivatives

Non-Antibiotic Drug Repositioning as an Alternative Antimicrobial Approach

The worldwide scenario of antibiotic resistance and the falling number of funds for the development of novel antibiotics have led research efforts toward the study of specific cost-effective strategies aimed at discovering drugs against microbial infections. Among the potential options, drug repositioning, which has already exhibited satisfactory results in other medical fields, came out as the most promising. It consists of finding new uses for previously approved medicines and, over the years, many “repurposed drugs” displayed some encouraging in vitro and in vivo results beyond their initial application. The principal theoretical justification for reusing already existing drugs is that they have known mechanisms of action and manageable side effects. Reuse of old drugs is now considered an interesting approach to overcome the drawbacks of conventional antibiotics. The purpose of this review is to offer the reader a panoramic view of the updated studies concerning the repositioning process of different classes of non-antibiotic drugs in the antimicrobial field. Several research works reported the ability of some non-steroidal anti-inflammatory drugs (NSAIDs), antidepressants, antipsychotics, and statins to counteract the growth of harmful microorganisms, demonstrating an interesting winning mode to fight infectious diseases caused by antimicrobial resistant bacteria

Evaluation of the Potential Protective Effect of Ellagic Acid against Heavy Metal (Cadmium, Mercury, and Lead) Toxicity in SH-SY5Y Neuroblastoma Cells

: Ellagic acid (EA), a polyphenolic constituent of plant origin, has been thoroughly investigated for its hypothesised pharmacological properties among which antioxidant and neuroprotective activities are included. The present study was designed to explore whether EA could attenuate heavy metal (cadmium, mercury, and lead)-induced neurotoxicity in SH-SY5Y cells, which were utilized as a model system for brain cells. MTT and LDH assays were performed to examine the viability of the SH-SY5Y cells after exposure to Cd, Hg, and Pb (either individually or in combination with EA) as well as the effects of necrotic cell death, respectively. Furthermore, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), a cell-based assay, was performed to determine whether EA could protect SH-SY5Y from heavy metal-induced oxidative stress. Results allowed us to assess the capability of EA to enhance the number of viable SH-SY5Y cells after exposure to heavy metal toxicity. Pre-treatment with EA showed a considerable, concentration-dependent, cytoprotective effect, particularly against Cd2+-induced toxicity. This effect was confirmed through the reduction of LDH release after the simultaneous cell treatment with Cd2+ and EA compared with Cd2+-treated cells. Furthermore, a significant, concentration-dependent decrease in reactive oxygen species (ROS) production, induced by H2O2 or heavy metals, was observed in the same model. Overall, the obtained results provide further insight into the protective role of EA against heavy metal-induced neurotoxicity and oxidative stress, thus indicating the potential beneficial effects of the consumption of EA-rich foods. However, to confirm its effects, well-designed human randomized controlled trials are needed to fill the existing gap between experimental and clinical research

Evaluation of the potential cytoprotective effect of Melatonin in comparison with Vitamin E and Trolox against Cd2+-Induced toxicity in SH-SY5Y, HCT 116, and HepG2 cell lines

Cadmium (Cd) toxicity poses a significant threat to cellular health, leading to oxidative stress and cell damage. Antioxidant agents, particularly those of natural origin, have been studied as a potential alternative for mitigating heavy metal toxicity. This study aimed to evaluate the cytoprotective effects of the antioxidant melatonin (MLT) in comparison with Vitamin E (VitE) and Trolox against Cd2+-induced cellular toxicity. The MTT assay was employed to assess cell viability in neuronal SH-SY5Y, colorectal HCT 116, and hepatic HepG2 cell lines. The results showed that all three antioxidants offered some level of protection against Cd toxicity, with Vitamin E proving to be the most effective. MLT also demonstrated a substantial cytoprotective effect, especially at the highest Cd concentration of 30 μM. These findings suggest that MLT, alongside Vit E and Trolox, could be valuable in mitigating the detrimental effects of Cd exposure by reducing the oxidative stress in these cellular models

Phenolic Compounds from Tropea Red Onion as Dietary Agents for Protection against Heavy Metals Toxicity

Abstract: The present study aims to highlight the cell protective effect of Tropea red onion (TRO) hydroalcoholic extract and some of its components against “non-essential” heavy metals. For this purpose, the cytoprotective roles of cyanidin, cyanidin-3-O-glucoside and quercetin against Cd, Hg and Pb and of TRO extract against Hg and Pb have been investigated, and data are reported here. To the best of our knowledge, this is the first detailed evaluation of the protective effect against cell damage induced by “non-essential” heavy metals through the simultaneous administration of cyanidin, cyanidin-3-O-glucoside and quercetin with CdCl2, HgCl2 or PbCl2 and the TRO extract against HgCl2 and PbCl2. Present data are also compared with our previous results from the TRO extract against Cd. The antioxidant capacity of the extract was also determined by the ferric reducing antioxidant power (FRAP) and the bovine brain peroxidation assay. Both of the assays indicated a good antioxidant capacity of the extract. Cell viability and the impact on necrotic cell death were examined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test and lactate dehydrogenase (LDH) release assay. After 24 h of exposure, Caco-2 cell viability decreased by approximately 50% at 0.25 μM for Cd, Hg and Pb and, after 72 h, the ranking order of “non-essential” heavy metal toxicity on cell viability was PbCl2 > CdCl2 > HgCl2. Cell viability was assessed by treating the cells with the biomolecules at doses of 25, 50 and 100 μg/mL for 24 and 72 h. The same analysis was carried out on Caco-2 cells treated with combinations of TRO extract, cyanidin, cyanidin-3-O-glucoside, or quercetin and “non-essential” heavy metals. Treatments with the bioactive metabolites did not significantly improve cell viability. The identical treatment of Caco-2 cells produced instead LDH release, suggesting a decrease in cell viability. Consistently with the finding that TRO extract showed a good antioxidant activity, we suggest that its higher cytotoxicity, compared to that of the individual assayed phytochemicals, may be derived by the combined antioxidant and chelating properties of all the molecules present in the extract. Therefore, from all the acquired experimental evidence, it appears that the TRO extract may be a better promising protective agent against the toxic effect of Cd, Hg and Pb compared to its bioactive metabolites

Carbazole Derivatives as STAT Inhibitors: An Overview

The carbazole class is made up of heterocyclically structured compounds first isolated from coal tar. Their structural motif is preponderant in different synthetic materials and naturally occurring alkaloids extracted from the taxonomically related higher plants of the genus Murraya, Glycosmis, and Clausena from the Rutaceae family. Concerning the biological activity of these compounds, many research groups have assessed their antiproliferative action of carbazoles on different types of tumoral cells, such as breast, cervical, ovarian, hepatic, oral cavity, and small-cell lung cancer, and underlined their potential effects against psoriasis. One of the principal mechanisms likely involved in these effects is the ability of carbazoles to target the JAK/STATs pathway, considered essential for cell differentiation, proliferation, development, apoptosis, and inflammation. In this review, we report the studies carried out, over the years, useful to synthesize compounds with carbazole moiety designed to target these kinds of kinases

Potential Protective Effects of Spirulina (Spirulina platensis) against In Vitro Toxicity Induced by Heavy Metals (Cadmium, Mercury, and Lead) on SH-SY5Y Neuroblastoma Cells

Spirulina, a filamentous microalga, is used all over the world as a nutraceutical dietary supplement. Recent studies have focused on examining its chelating activity and antioxidant properties, especially as a candidate for protection against neurotoxicity caused by heavy metals. The MTT test and LDH assay were used to examine the viability of the SH-SY5Y cells for 24, 48, and 72 h, to Cd, Hg, and Pb, individually or in combination with Spirulina, and the effects of necrotic cell death. In comparison to the control group, the viability of SH-SY5Y cells decreased after 24 h of exposure, with Cd being more toxic than Hg and Pb being less lethal. The effects of heavy metal toxicity on cell survival were ranked in order after 72 h under identical experimental circumstances as follows: Hg, Pb, and Cd. The viability of the cells was then tested after being exposed to Spirulina at doses of 5 at 50 (%v/v) for 24, 48, and 72 h, respectively. SH-SY5Y cells that had been treated with mixtures of heavy metals and Spirulina underwent the same assay. Cell viability is considerably increased by using Spirulina treatments at the prescribed periods and doses. Instead, the same procedure, when applied to SH-SY5Y cells, caused the release of LDH, which is consistent with the reduction in cell viability. We demonstrated for the first time, considering all the available data, that Spirulina 5, 25, and 50 (%v/v) enhanced the number of viable SH-SY5Y cells utilized as a model system for brain cells. Overall, the data from the present study provide a first insight into the promising positive role of Spirulina against the potentially toxic effects of metals