Scavenging Effect of Various Extracts of the Gymnema sylvestre R. Br. and Antioxidant Activity of the Isolated Triterpenes

Gymnema sylvestre has been used in Asian traditional medicine for its anti-microbial, antihypercholesterolemic, hepatoprotective and sweet suppressing properties and activities. G. sylvestre has also been used extensively in chewing gum, as a health food for preventing obesity and diabetes, and as a tea. This study has evaluated the total phenolic content and antioxidant activity of the aqueous and organic G. sylvestre extracts and their sub-fractions for the initial characterization of the biological properties of the isolated compounds. An in vivo cell model was used to calculate the concentration inhibiting cell growth by 50% and the ability to exert antioxidant activity. All compounds inhibit cell growth in a dose-dependent manner, with an IC50 value ranging between 29 and 1462 μM. The effects on intracellular ROS levels are extremely variable, but it is of interest that some of the compounds appear to display an antioxidant effect

Effects of Dried Blood Spot Storage on Lipidomic Analysis

During the lipidomic analysis of red blood cell membranes, the distribution and percentage ratios of the fatty acids are measured. Since fatty acids are the key constituents of cell membranes, by evaluating their quantities it possible to understand the general health of the cells and to obtain health indicators of the whole organism. However, because the analysis is precise, it is necessary to ensure that the blood does not undergo significant variations between the point of collection and analysis. The composition of the blood may vary dramatically weeks after collection, hence, here an attempt is made to stabilize these complex matrixes using antioxidants deposited on the paper cards on which the blood itself is deposited

Gymnema sylvestre R. Br., an Indian medicinal herb: traditional uses, chemical composition, and biological activity

Gymnema sylvestre R. Br. is one of the most important medicinal plants that grows in tropical forests in India and South East Asia. Its active ingredients and extracts of leaves and roots are used in traditional medicine to treat various ailments and they are present in the market for pharmaceutical and parapharmaceutical products. Commercial products based on substances of plant origin that are generally connoted as natural have to be subjected to monitoring and evaluation by health authorities for their potential impacts on public health. The monitoring and evaluation of these products are critical because the boundary between a therapeutic action and a functional or healthy activity has not yet been defined in a clear and unambiguous way. Therefore, these products are considered borderline products, and they require careful and rigorous studies, in order to use them as complement and/or even replacement of synthetic drugs that are characterized by side effects and high economic costs. This review explores the traditional uses, chemical composition and biological activity of G. sylvestre extracts, providing a general framework on the most interesting extracts and what are the necessary studies for a complete definition of the range of activities

New findings on the d(TGGGAG) sequence: Surprising anti-HIV-1 activity

The biological relevance of tetramolecular G-quadruplexes especially as anti-HIV agents has been extensively reported in the literature over the last years. In the light of our recent results regarding the slow G-quadruplex folding kinetics of ODNs based on d(TGGGAG) sequence, here, we report a systematic anti-HIV screening to investigate the impact of the G-quadruplex folding on their anti-HIV activity. In particular, varying the single stranded concentrations of ODNs, it has been tested a pool of ODN sample solutions with different G-quadruplex concentrations. The anti-HIV assays have been designed favouring the limited kinetics involved in the tetramolecular G4-association based on the d(TGGGAG) sequence. Aiming to determine the stoichiometry of G-quadruplex structures in the same experimental conditions of the anti-HIV assays, a native gel electrophoresis was performed. The gel confirmed the G-quadruplex formation for almost all sample solutions while showing the formation of high order G4 structures for the more concentrated ODNs solutions. The most significant result is the discovery of a potent anti-HIV activity of the G-quadruplex formed by the natural d(TGGGAG) sequence (IC50 = 14 nM) that, until now, has been reported to be completely inactive against HIV infection

Synthesis of Oligonucleotide Conjugates and Phosphorylated Nucleotide Analogues: An Improvement to a Solid Phase Synthetic Approach

An improvement to our solid phase strategy to generate pharmacologically interesting molecule libraries is proposed here. The synthesis of newo-chlorophenol-functionalised solid supports with very high loading (0.18–0.22 meq/g for control pore glass (CPG) and 0.25–0.50 meq/g for TG) is reported. To test the efficiency of these supports, we prepared nucleotide and oligonucleotide models, and their coupling yields and the purity of the crude detached materials were comparable to previously available results. These supports allow the facile and high-yield preparation of highly pure phosphodiester and phosphoramidate monoester nucleosides, conjugated oligonucleotides, and other yet unexplored classes of phosphodiester and phosphoramidate molecules

New silibinin glyco-conjugates: Synthesis and evaluation of antioxidant properties

New silibinin glyco-conjugates have been synthesized by efficient method and in short time. Exploiting our solution phase strategy, several structurally diverse silibinin glyco-conjugates (gluco, manno, galacto, and lacto-) were successfully realized in very good yields and in short time. In preliminary study to evaluate their antioxidant and neuroprotective activities new derivatives were subjected to DPPH free radical scavenging assay and the Xanthine oxidase (XO) inhibition models assay. Irrespective of the sugar moiety examined, new glyco-conjugates are more than 50 times water-soluble of silibinin. In the other hand they exhibit a radical scavenging activities slightly higher than to silibinin and XO inhibition at least as silibinin. (C) 2014 Elsevier Ltd. All rights reserved

Disinfection by-Products and Ecotoxic Risk Associated with Hypochlorite Treatment of Tramadol

In recent years, many studies have highlighted the consistent finding of tramadol (TRA) in the effluents from wastewater treatment plants (WTPs) and also in some rivers and lakes in both Europe and North America, suggesting that TRA is removed by no more than 36% by specific disinfection treatments. The extensive use of this drug has led to environmental pollution of both water and soil, up to its detection in growing plants. In order to expand the knowledge about TRA toxicity as well as the nature of its disinfection by-products (DBPs), a simulation of the waste treatment chlorination step has been reported herein. In particular, we found seven new by-products, that together with TRA, have been assayed on different living organisms (Aliivibrio fischeri, Raphidocelis subcapitata and Daphnia magna), to test their acute and chronic toxicity. The results reported that TRA may be classified as a harmful compound to some aquatic organisms whereas its chlorinated product mixture showed no effects on any of the organisms tested. All data suggest however that TRA chlorination treatment produces a variety of DBPs which can be more harmful than TRA and a risk for the aquatic environment and human health

Herbicidal potential of phenolic and cyanogenic glycoside compounds isolated from Mediterranean plants

This study was conducted to test five phenolic and cyanogenic glycoside compounds for growth regulating activity on the germination and seedling growth of Portulaca oleracea L., Amaranthus retroflexus L., and Lactuca sativa L. at different concentrations. Overall, the tested compounds revealed growth-regulating activity in species-specific and concentration dependent manner. The most powerful effects were much pronounced on seedling growth rather than on germination. In fact, the compounds 1 (amygdalin) and 2 (salicylic acid) were the most phytotoxic on root growth of  P. oleracea, and they caused, respectively, an inhibition of 55% and 85% at 10-6 M and 10-4 M. On the other hand, the lettuce seedling growth was more sensitive than weeds growth to the compounds 4 (3,4,5-trihydroxybenzoic acid) and 5 (7-hydroxycoumarin), which exhibited a moderate inhibition at the highest concentration. This selectivity and specificity of these active allelopathic compounds could be very useful for the development of new application of natural substances to control the aggressive weeds. Thus, our findings suggest that the integration of these compounds may maintain irrigation system and reduce the massive use of agrochemicals in agro-ecosystems

Polyphenolic profile and targeted bioactivity of methanolic extracts from mediterranean ethnomedicinal plants on human cancer cell lines

The methanol extracts of the aerial part of four ethnomedicinal plants of Mediterranean region, two non-seed vascular plants, Equisetum hyemale L. and Phyllitis scolopendrium (L.) Newman, and two Spermatophyta, Juniperus communis L. (J. communis) and Cotinus coggygria Scop. (C. coggygria), were screened against four human cells lines (A549, MCF7, TK6 and U937). Only the extracts of J. communis and C. coggygria showed marked cytotoxic effects, affecting both cell morphology and growth. A dose-dependent effect of these two extracts was also observed on the cell cycle distribution. Incubation of all the cell lines in a medium containing J. communis extract determined a remarkable accumulation of cells in the G2/M phase, whereas the C. coggygria extract induced a significant increase in the percentage of G1 cells. The novelty of our findings stands on the observation that the two extracts, consistently, elicited coherent effects on the cell cycle in four cell lines, independently from their phenotype, as two of them have epithelial origin and grow adherent and two are lymphoblastoid and grow in suspension. Even the expression profiles of several proteins regulating cell cycle progression and cell death were affected by both extracts. LC-MS investigation of methanol extract of C. coggygria led to the identification of twelve flavonoids (compounds 1–11, 19) and eight polyphenols derivatives (12–18, 20), while in J. communis extract, eight flavonoids (21–28), a α-ionone glycoside (29) and a lignin (30) were found. Although many of these compounds have interesting individual biological activities, their natural blends seem to exert specific effects on the proliferation of cell lines either growing adherent or in suspension, suggesting potential use in fighting cancer

Silybins inhibit human IAPP amyloid growth and toxicity through stereospecific interactions

Type 2 Diabetes is a major public health threat, and its prevalence is increasing worldwide. The abnormal accumulation of islet amyloid polypeptide (IAPP) in pancreatic β-cells is associated with the onset of the disease. Therefore, the design of small molecules able to inhibit IAPP aggregation represents a promising strategy in the development of new therapies. Here we employ in vitro, biophysical, and computational methods to inspect the ability of Silybin A and Silybin B, two natural diastereoisomers extracted from milk thistle, to interfere with the toxic self-assembly of human IAPP (hIAPP). We show that Silybin B inhibits amyloid aggregation and protects INS-1 cells from hIAPP toxicity more than Silybin A. Molecular dynamics simulations revealed that the higher efficiency of Silybin B is ascribable to its interactions with precise hIAPP regions that are notoriously involved in hIAPP self-assembly i.e., the S20-S29 amyloidogenic core, H18, the N-terminal domain, and N35. These results highlight the importance of stereospecific ligand-peptide interactions in regulating amyloid aggregation and provide a blueprint for future studies aimed at designing Silybin derivatives with enhanced drug-like properties. Keywords: Aggregation; Diabetes; Inhibitors; Molecular dynamics; Peptid