Phytochemical study of Joannesia princeps Vell. (Euphorbiaceae) leaves

A phytochemical study of chloroform-methanol and methanol extracts of Joannesia princeps Vell. leaves led to the isolation of twenty eight compounds, including two α-ionones (2, 5), three glycosylated monoterpenes (1, 3, 4), eight phenolic compounds (6, 8, 9, 12, 14, 17, 18, 24), two gallotannins (10, 11), twelve flavonoids (7, 15, 16, 19, 20-23, 25-28), and one lignan (13). The structural characterization of the isolated compounds was performed by spectroscopic data and comparison with the literature. All compounds were isolated from this species and from the genus Joannesia for the first time. The chemotaxonomic importance of these metabolites is therefore summarized

Natural compounds as inhibitors of lactate dehydrogenase

Lactate dehydrogenase (LDH) catalyses the conversion of pyruvate to lactate, utilizing NADH as co-factor. It’s a tetrameric enzyme composed of two subunits, M and H, whose association can generate five isoforms. One of this, the human isoform 5, hLDH5 has the highest activity in converting pyruvate to lactate under anaerobic conditions, such as those found in hypoxic tumors and for this reason it’s up-regulated in tumor tissues where cells glycolytic rate is up to 200 times higher than that of the normal tissue. hLDH5 inhibition should cause cancer cell death by starvation, without interfering with healthy cells that normally use oxidative phosphorylation for ATP generation (1). Inhibition of LDH is so considered as a promising target in cancer treatment, and natural compounds could serve as useful scaffold to study new anticancer agents. Among the few plant derived hLDH5 inhibitors already investigated there are mainly phenolic derivatives such as gossypol, morin, and galloflavin (2,3). In the last decade our research group successfully detected a good number of compounds obtained from Mediterranean plants with anticancer effect, and for this reason start a research program aimed to discover new classes of natural products having hLDH5 inhibitory activity. In a first study, since some species of Phlomis (Lamiaceae) proved to possess anti-cancer properties, the crude extract of P. kurdica aerial parts was selected as the starting material. Two new flavonoids and one new phenylpropanoid, together with eleven known phenolic compounds, including flavonoids and phenylpropanoids were isolated and assayed for their hLDH5 inhibitory activity. Luteolin 7-O-β-D-glucopyranoside showed an IC50 value similar to that of reference compound galloflavin (4). Then, since Polygala genus (Polygalaceae) is well known to contain phenolic oligosaccharides, xanthones, lignans, and triterpenic saponins and it’s largely used in the traditional medicine, an Italian species P. flavescens subsp. flavescens was chosen. Ten new compounds were isolated from the methanol residue of the aerial parts through Sephadex and RP-HPLC separations, including four flavonol glycosides, two oligosaccharides, one α-ionone, and three triterpenoidic saponins, together with two known oligosaccharides and two flavonol glycosides. The isolates were assayed for their inhibitory activity against hLDH5 and 3,6'-di-O-sinapoylsucrose showed an inhibition potency comparable or even slightly better than reference inhibitor galloflavin. Docking studies were carried out to hypothesize the interaction mode of active compounds in the enzyme active site

Inhibitors of lactate dehydrogenase (hLDH5) from Polygala flavescens subsp. flavescens

The human isoform 5 of lactate dehydrogenase (hLDH5) is an enzyme up-regulated in tumor tissues since cancer cells depend mainly on anaerobic respiration and their glycolytic rate is up to 200 times higher than that of the normal tissue. hLDH5 inhibition should cause cancer cell death by starvation, without interfering with healthy cells that normally use oxidative phosphorylation for ATP generation. Inhibition of LDH is so considered as a promising target in cancer treatment, since it is possible to cause a starving of cancerous cells by reducing glycolysis or by inhibiting the conversion of glucose to lactate. In the course of our research program on the hLDH5 inhibitory activity of natural products [1], a chemical study of P. flavescens subsp. flavescens was carried out. Polygala L. genus (Polygalaceae) is well known to contain phenolic oligosaccharides, xanthones, lignans, and triterpenic saponins and it’s largely used in the traditional medicine [2]. Ten new compounds were isolated from the n-BuOH residue of the aerial parts through Sephadex and RP-HPLC separations, including four flavonol glycosides, two oligosaccharides, one α-ionone, and three triterpenoidic saponins, together with two known oligosaccharides and two flavonol glycosides. All structures were elucidated on the basis of their spectroscopic and spectrometric data. The isolates were assayed for their inhibitory activity against hLDH5 and 3,6'-di-O-sinapoylsucrose showed an IC50 value of 90.4 µM. Modeling studies were carried out to suggest the putative interaction mode of this compound in the enzyme active site. This analysis highlighted that 3,6'-di-O-sinapoylsucrose shows a high number of H-bonds and interacts with enzyme regions rarely explored by the known hLDH5 inhibitors

Inhibition of p38 MAP kinase pathway induces apoptosis and prevents Epstein Barr virus reactivation in Raji cells exposed to lytic cycle inducing compounds

BACKGROUND: EBV lytic cycle activators, such as phorbol esters, anti-immunoglobulin, transforming growth factor β (TGFβ), sodium butyrate, induce apoptosis in EBV-negative but not in EBV-positive Burkitt's lymphoma (BL) cells. To investigate the molecular mechanisms allowing EBV-infected cells to be protected, we examined the expression of viral and cellular antiapoptotic proteins as well as the activation of signal transduction pathways in BL-derived Raji cells exposed to lytic cycle inducing agents. RESULTS: Our data show that, following EBV activation, the latent membrane protein 1 (LMP1) and the cellular anti-apoptotic proteins MCL-1 and BCL-2 were quickly up-regulated and that Raji cells remained viable even when exposed simultaneously to P(BU)(2), sodium butyrate and TGFβ. We report here that inhibition of p38 pathway, during EBV activation, led to a three fold increment of apoptosis and largely prevented lytic gene expression. CONCLUSION: These findings indicate that, during the switch from the latent to the lytic phase of EBV infection, p38 MAPK phosphorylation plays a key role both for protecting the host cells from apoptosis as well as for inducing viral reactivation. Because Raji cells are defective for late antigens expression, we hypothesize that the increment of LMP1 gene expression in the early phases of EBV lytic cycle might contribute to the survival of the EBV-positive cells

Interactive Effects of Genotype and Molybdenum Supply on Yield and Overall Fruit Quality of Tomato

Molybdenum (Mo) is an essential trace element for plant growth, development, and production. However, there is little known about the function and effects of molybdenum in tomato plants. The present study assessed the influences of different Mo concentrations on four tomato F1 hybrids (“Bybal” F1, “Tyty” F1, “Paride” F1, and “Ornela” F1) grown using a soilless system with different Mo levels [0.0, 0.5 (standard NS), 2.0, and 4.0 μmol L−1, respectively]. The crop yield, plant vigor, fruit skin color, TA, fruit water content as well as the accumulation of SSC, and some antioxidant compounds such as lycopene, polyphenols and ascorbic acid were evaluated. The minerals concentration, including nitrogen (N), Mo, iron (Fe), and copper (Cu), were measured in tomato fruits. Results revealed that tomato plants grown with 2.0 μmol Mo L−1 compared to plants grown with 0.5 μmol Mo L−1 incurred a significant increase of total yield by 21.7%, marketable yield by 9.1%, aboveground biomass by 16.7%, plant height at 50 DAT by 6.5%, polyphenol content by 3.5%, ascorbic acid by 1.0%, SSC by 3.5%, N fruit content by 24.8%, Mo fruit content by 20.0%, and Fe fruit content by 60.5%. However, the Mo concentration did not significantly influence the average fruit weight, b* fruit skin color coordinate and TA. Furthermore, tomato fruits from plants grown with 2.0 μmol Mo L−1 showed a lower Cu fruit content (16.1%) than fruits from plants grown with 0.5 μmol Mo L−1 (standard NS). Consequently, our study highlights the different behavior of the tomato genotypes tested when subjected to different levels of Mo concentration in the nutrient solution. Nevertheless, taking all in consideration our results clearly suggest that a Mo fertilization of 2.0 μmol Mo L−1 effectively enhance crop performance and overall fruit quality of tomato

Antioxidant and Antisenescence Effects of Bergamot Juice

Aging is one of the main risk factor for the onset of cardiovascular diseases; one of the possible explanations could be linked to the age-associated overproduction of free radicals. This increase of oxidative stress can be overcome with a high intake of food antioxidants. In this context, a number of studies have been addressed to assess the antiaging potential of natural antioxidant compounds. Recently, it has been shown that the juice of bergamot (Citrus bergamia Risso et Poiteau), a fruit mostly produced in the Ionian coastal areas of Southern Italy (Calabria), is a valuable source of health-promoting constituents with, among other, antioxidant properties. In order to investigate the potential antiaging effects of this Mediterranean natural antioxidant source, bergamot juices of three different cultivars ("fantastico," "femminello," and "castagnaro") were herein characterized by the mean of high-performance liquid chromatography-photodiode array-electrospray ionization-tandem mass spectrometry. Then, juices were investigated for the evaluation of total polyphenolic and flavonoid contents, cell-free model antioxidant activities, and in vitro antiaging properties on two different cellular models of induced myocardial senescence. The best performing juice was also assessed in vivo. The phytochemical profiles confirmed that juices were rich in flavonoids, both flavone and flavanone glycosides. In addition, two limonoid glycosides were also identified in all cultivars. Each cultivar showed different phenolic and flavonoid contents. In tube results showed the juice robust antioxidant activities that correlate with their phenolic and flavonoid contents. Moreover, for the first time, the ability of juice to counteract the chemical-induced senescence was here demonstrated in both cellular models. Lastly, the in vivo data obtained from mouse hearts evidenced an increase in transcription of genes involved in antiaging and antioxidant responses. The overall results suggest that bergamot juice exerts antioxidant and antisenescence effects, making it useful for nutraceutical purposes

Negative effects of a high tumour necrosis factor-α concentration on human gingival mesenchymal stem cell trophism: The use of natural compounds as modulatory agents

Background: Adult mesenchymal stem cells (MSCs) play a crucial role in the maintenance of tissue homeostasis and in regenerative processes. Among the different MSC types, the gingiva-derived mesenchymal stem cells (GMSCs) have arisen as a promising tool to promote the repair of damaged tissues secreting trophic mediators that affect different types of cells involved in regenerative processes. Tumour necrosis factor (TNF)-α is one of the key mediators of inflammation that could affect tissue regenerative processes and modify the MSC properties in in-vitro applications. To date, no data have been reported on the effects of TNF-α on GMSC trophic activities and how its modulation with anti-inflammatory agents from natural sources could modulate the GMSC properties. Methods: GMSCs were isolated and characterized from healthy subjects. The effects of TNF-α were evaluated on GMSCs and on the well-being of endothelial cells. The secretion of cytokines was measured and related to the modification of GMSC-endothelial cell communication using a conditioned-medium method. The ability to modify the inflammatory response was evaluated in the presence of Ribes nigrum bud extract (RBE). Results: TNF-α differently affected GMSC proliferation and the expression of inflammatory-related proteins (interleukin (IL)-6, IL-10, transforming growth factor (TGF)-β, and cyclooxygenase (COX)-2) dependent on its concentration. A high TNF-α concentration decreased the GMSC viability and impaired the positive cross-talk between GMSCs and endothelial cells, probably by enhancing the amount of pro-inflammatory cytokines in the GMSC secretome. RBE restored the beneficial effects of GMSCs on endothelial viability and motility under inflammatory conditions. Conclusions: A high TNF-α concentration decreased the well-being of GMSCs, modifying their trophic activities and decreasing endothelial cell healing. These data highlight the importance of controlling TNF-α concentrations to maintain the trophic activity of GMSCs. Furthermore, the use of natural anti-inflammatory agents restored the regenerative properties of GMSCs on endothelial cells, opening the way to the use and development of natural extracts in wound healing, periodontal regeneration, and tissue-engineering applications that use MSCs

Palliative care in the emergency department as seen by providers and users: a qualitative study

Background Much effort has been made to explore how patients with advanced chronic illness and their families experience care when they attend the Emergency Department, and many studies have investigated how healthcare professionals perceive Palliative Care provision in the Emergency Department. Various models exist, but nonetheless incorporating palliative care into the Emergency Department remains challenging. Considering both healthcare professionals\u2019 and users\u2019 perspective on problems encountered in delivering and receiving appropriate palliative care within this context may provide important insight into meaningful targets for improvements in quality of care. Accordingly, this study aims at exploring issues in delivering palliative care in the Emergency Department from the perspective of both providers and users, as part of a larger project on the development and implementation of a quality improvement program in Italian Emergency Departments. Methods A qualitative study involving focus group interviews with Emergency Department professionals and semi-structured interviews with patients with palliative care needs in the Emergency Department and their relatives was conducted. Both datasets were analyzed using Thematic Analysis. Results Twenty-one healthcare professionals, 6 patients and 5 relatives participated in this study. Five themes were identified: 1) shared priorities in Emergency Department among healthcare professionals and patients, 2) the information provided by healthcare professionals and that desired by relatives, 3) perception of environment and time, 4) limitations and barriers to the continuity of care, and 5) the contrasting interpretations of giving and receiving palliative care. Conclusions This study provides insights into targets for changes in Italian Emergency Departments. Room for improvement relates to training for healthcare professionals on palliative care, the development of a shared care pathway for patients with palliative care needs, and the optimization of Emergency Department environment. These targets will be the basis for the development of a quality improvement program in Italian Emergency Departments