USE OF NOVEL PSYCHOACTIVE SUBSTANCES (NPS) OF NATURAL ORIGIN: AN INTERNATIONAL SURVEY

Aim NPS recreational use are mostly derived and modified from constituents of natural origin. Here we investigated the motivation of natural NPS use, perception of potential associated health risks and demographic factors associated with natural NPS use. Methodology The Bristol Online Survey was in English and advertised on the drug forum Bluelight and social media Facebook pages and via University email between 1 July and 17 November 2018 (812 responses; 458 NPS users). This pharmacoepidemiologic study was evaluated using SPSS software (IBM SPSS Statistics version 24;MacOS Sierra 10.12.3). Results The main motivation (67%) for natural NPS use was curiosity to ‘’experience something new and different’’ with a low perception of health risk (85%). The preferred natural NPS was magic mushrooms (psilocybin, 95%) often in combination with cannabis (63%). Gender, living area, educational background, smoking frequency and employment significantly affected (P<0.001) natural NPS use. Male respondents, residents of suburban and rural areas, smokers and respondents with low educational level represented the majority of natural NPS users as well as the employed, the unable to work and retired groups. Similarly, sexual orientation significantly affected (p<0.05) natural NPS use. Conclusion Users’ low perception of natural NPS safety profile and the fact that natural NPS use correlates with a lower level of education, indicates a need for enhanced statutory targeted prevention interventions in schools. Many users (67%) reported natural NPS make them happier and more optimistic about life emphasizing the need to study the potential application of these substances in appropriate clinical settings for therapeutic purposes in mental health.Peer reviewe

Over-expression of a tomato N-acetyl-L-glutamate synthase gene (SlNAGS1) in Arabidopsis thaliana results in high ornithine levels and increased tolerance in salt and drought stresses

A single copy of the N-acetyl-L-glutamate synthase gene (SlNAGS1) has been isolated from tomato. The deduced amino acid sequence consists of 604 amino acids and shows a high level of similarity to the predicted Arabidopsis NAGS1 and NAGS2 proteins. Furthermore, the N-terminus ArgB domain and the C-terminus ArgA domain found in SlNAGS1 are similar to the structural arrangements that have been reported for other predicted NAGS proteins. SlNAGS1 was expressed at high levels in all aerial organs, and at basic levels in seeds, whereas it was not detected at all in roots. SlNAGS1 transcript accumulation was noticed transiently in tomato fruit at the red-fruit stage. In addition, an increase of SlNAGS1 transcripts was detected in mature green tomato fruit within the first hour of exposure to low oxygen concentrations. Transgenic Arabidopsis plants have been generated expressing the SlNAGS1 gene under the control of the cauliflower mosaic virus (CaMV) 35S promoter. Three homozygous transgenic lines expressing the transgene (lines 1-7, 3-8, and 6-5) were evaluated further. All three transgenic lines showed a significant accumulation of ornithine in the leaves with line 3-8 exhibiting the highest concentration. The same lines demonstrated higher germination ability compared to wild-type (WT) plants when subjected to 250 mM NaCl. Similarly, mature plants of all three transgenic lines displayed a higher tolerance to salt and drought stress compared to WT plants. Under most experimental conditions, transgenic line 3-8 performed best, while the responses obtained from lines 1-7 and 6-5 depended on the applied stimulus. To our knowledge, this is the first plant NAGS gene to be isolated, characterized, and genetically modified

Exploring the Ecological Preferences and Essential Oil Variability in Wild-Growing Populations of the Endangered Local Greek Endemic <i>Thymus holosericeus</i> (Lamiaceae)

Thymus holosericeus Čelak. (Lamiaceae) is a taxonomically isolated and endangered local endemic thyme species which is geographically isolated in four Ionian Islands (West Greece). The present study investigated the essential oil (EO) composition, the ecological preferences, and their correlations in three T. holosericeus wild-growing populations from Zakynthos (ΤH-Z), Cephalonia (ΤH-C) and Lefkada (ΤH-L). The variations in essential oil yield and the composition of T. holosericeus populations were evaluated using hydrodistillation, GC/MS, TLC and NMR analysis. The climatic conditions of each sample were organized and analyzed in RStudio with the raster package and in SPSS with Pearson’s Canonical Correlation Analysis (CCA), respectively. The aerial parts of the plants varied in EO yields from 1.92 to 2.28% w/v. The analysis of EO constituents revealed noteworthy qualitative and quantitative inter-population variation. The composition of EOs revealed the presence of linalool (82.77%) and borneol (5.95%) as major compounds in ΤH-Z, while carvacrol (35.34%), geraniol (23.98%), linalool (14.37%), borneol (5.66%), thymol (4.27%) and p-cymene (4.08%) were the main compounds in ΤH-C and linalool (40.37%), geraniol (39.42%) and borneol (5.20%) were dominant components in ΤH-L. The results of the gas chromatography procedure have also been confirmed by 1H and 13C-NMR and TLC analysis. The ecological profile showed an average annual precipitation of 942 ± 18.33 mm and the temperature limits in which T. holosericeus seems to adapt to are 6.80± 1.08 °C 27.70 ± 0.70 °C. Regarding the examined samples, TH-C was adapted to the driest summer and coldest winter conditions, TH-Z was adapted to the lowest annual precipitation with the most complex climatic conditions, and TH-L was adapted to the highest summer temperatures with the lowest precipitation in the wettest period of the year. For each sampled population, the CCA identified the association of the samples’ EOs composition with the prevailing local environmental conditions

Ecological Preferences and Diversity of Essential Oil Composition in Endangered Wild-Growing Populations of <i>Sideritis sipylea</i> Boiss. (Lamiaceae) of the East Aegean Islands (Greece): Evidencing Antioxidant Potential, Antimicrobial and Cytotoxic Activities

Plants from the genus Sideritis (Lamiaceae) have been widely used in folk medicine for a long time and consequently are a focus of the scientific community. Despite this interest, explicit data about the essential oils (EOs) of the Endangered Sideritis sipylea have not been readily available to date. In this study, we investigated the ecological preferences of Greek S. sipylea and the chemical composition of the essential oils of wild-growing S. sipylea populations from two Greek islands (S1: Samos, S2: Lesvos); we explored concomitant associations with environmental factors; and we assessed their (i) antioxidant potential (two tests), (ii) antimicrobial activity against six microbial and two fungal strains, and (iii) cytotoxic effect in two human and one murine cell lines. We compiled an ecological profile in R based on all known Greek localities of S. sipylea, outlining for the first time its preferences regarding temperature (3.48 ± 1.53 °C to 30.70 ± 1.11 °C) and the precipitation regimes (5.92 ± 2.33 mm to 136 ± 11.43 mm) shaping its natural occurrence in the wild. The chemical analysis (42 compounds in total) confirmed the domination of monoterpene hydrocarbons in both samples (with quantitative and qualitative differences) and identified 12 new constituents reported in S. sipylea for the first time (e.g., Bicyclogermacrene and Cumacrene). Dominant compounds in S1 (39 constituents) were β-Myrcene (20.4%) followed by β-caryophyllene (11.8%), bicyclogermacrene (7.1%), β-pinene (6.3%), carvacrol (6.2%) and α-terpinene (6.1%), whereas in S2 (26 constituents) the main ones were α-pinene (37.3%), β-pinene (15.1%) and sabinene (12.1%), followed by β-caryophyllene (5.6%) and bicyclogermacrene (5.5%). The strong antioxidant capacity and cytotoxic activity of S. sipylea EOs are reported herein for the first time, while new insight is provided regarding their effect on bacterial and fungal strains (four ones originally tested herein). The biological activity analysis demonstrated variation among samples, with S2 being more potent than S1. Altogether, the results of the present study demonstrate the high biological potential of S. sipylea EOs with an interesting antioxidant capacity and antimicrobial and cytotoxic effects and reveal associations of natural chemodiversity with climatic factors

Phytochemical analysis with the antioxidant and aldose reductase inhibitory capacities of <i>Tephrosia humilis</i> aerial parts’ extracts

<p>The aerial parts of <i>Tephrosia humilis</i> were tested about their antioxidant potential, their ability to inhibit the aldose/aldehyde reductase enzymes and their phenolic content. The plant material was exhaustively extracted with petroleum ether, dichloromethane and methanol, consecutively. The concentrated methanol extract was re-extracted, successively, with diethyl ether, ethyl acetate and n-butanol. All extracts showed significant antioxidant capacity, but the most effective was the ethyl acetate extract. As about the aldose reductase inhibition, all fractions, except the aqueous, were strong inhibitors of the enzyme, with the n-butanolic and ethyl acetate fractions to inhibit the enzyme above 75%. These findings provide support to the ethnopharmacological usage of the plant as antioxidant and validate its potential to act against the long-term diabetic complications. The phytochemical analysis showed the presence of 1,4-dihydroxy-3,4-(epoxyethano)-5-cyclohexene(<b>1</b>), cleroindicin E(<b>2</b>), lupeol(<b>3</b>), methyl p-coumarate(<b>4</b>), methyl 4-hydroxybenzoate(<b>5</b>), prunin(<b>6</b>), 5,7,2ʹ,5ʹ-tetrahydroxyflavanone 7-rutinoside(<b>7</b>), protocatechuic acid(<b>8</b>), luteolin 7-glucoside(<b>9</b>), apigenin(<b>10</b>), naringin(<b>11</b>), rhoifolin(<b>12</b>) and luteolin 7-glucuronate(<b>13</b>).</p

Antioxidant and antiinflammatory activities of Sideritis perfoliata subsp perfoliata (Lamiaceae)

Sideritis perfoliata L. subsp. perfoliata is a plant widely used in folk medicine in Greece since antiquity because of its antiinflammatory, antirheumatic, antiulcer, digestive and vasoprotective properties. Phytochemical investigations of the polar extracts afforded four flavonoid glycosides, four phenylpropanoic glycosides, caffeic acid and one iridoid, ajugoside. Reactive oxygen species (ROS) are implicated in the aetiology of several inflammatory processes. In the present study polar fractions and isolated compounds from S. perfoliata subsp. perfoliata were evaluated for their antioxidant activity using DPPH spectrophotometric and TBA lipid peroxidation assays, as well as for their antiinflammatory activity using the soybean lipoxygenase bioassay. All extracts and isolated compounds showed significant antioxidant and inhibitory activity against soybean lipoxygenase. These findings give support to the ethnopharmacological use of the plant in the treatment of several inflammatory ailments. Copyright (c) 2008 John Wiley &amp; Sons, Ltd

Phenolic compounds with antioxidant activity from Anthemis tinctoria L. (Asteraceae)

From the aerial parts of Anthemis tinctoria L. subsp. tinctoria var. pallida DC. (Asteraceae), one new cyclitol glucoside, conduritol F-1-O-(6'-O-E-p-caffeoyl)-beta -D-glucopyranoside (1), has been isolated together with four flavonoids, nicotiflorin (2), isoquercitrin (3), rutin (4) and patulitrin (5). The structures of the isolated compds. were established by means of NMR, MS, and UV spectral analyses. Methanolic ext. and pure isolated compds. were examd. for their free radical, scavenging activity, using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free stable radical, and for their inhibitory activity toward soybean lipoxygenase, using linoleic acid as substrate. Compds. 1 and 5 showed a strong scavenging effect in the DPPH radical assay. In addn. 5 also exhibited high inhibitory activity on soybean lipoxygenase

An NF-&kappa;B- and Therapy-Related Regulatory Network in Glioma: A Potential Mechanism of Action for Natural Antiglioma Agents

High-grade gliomas are among the most aggressive malignancies, with significantly low median survival. Recent experimental research in the field has highlighted the importance of natural substances as possible antiglioma agents, also known for their antioxidant and anti-inflammatory action. We have previously shown that natural substances target several surface cluster of differentiation (CD) markers in glioma cells, as part of their mechanism of action. We analyzed the genome-wide NF-&kappa;B binding sites residing in consensus regulatory elements, based on ENCODE data. We found that NF-&kappa;B binding sites reside adjacent to the promoter regions of genes encoding CD markers targeted by antiglioma agents (namely, CD15/FUT4, CD28, CD44, CD58, CD61/SELL, CD71/TFRC, and CD122/IL2RB). Network and pathway analysis revealed that the markers are associated with a core network of genes that, altogether, participate in processes that associate tumorigenesis with inflammation and immune evasion. Our results reveal a core regulatory network that can be targeted in glioblastoma, with apparent implications in individuals that suffer from this devastating malignancy

Seasonal Variation of Aromatic Plants under Cultivation Conditions

In this study, five plant species, members of the Lamiaceae family, namely Salvia officinalis L., Salvia rosmarinus&nbsp;Spenn, Mentha &times; piperita L., Mentha spicata L. and Origanum vulgare subsp. hirtum (Link) Ietswaart, were studied for the influence of harvesting time on the herb crop yield, the volatile compounds (EOs) content/yield and their chemical composition. EOs were isolated by means of hydro-distillation from different plant parts at different growth stages. Their components were analyzed by gas chromatography coupled with mass spectrometry (GC-MS). The highest yields of EOs were obtained at the full flowering stage and important changes were observed in their composition. The fluctuations in the percentage composition of the major compounds in the EOs, throughout harvesting time, were observed at camphor/&alpha;-thujone for S. officinalis, camphor/1,8-cineole for S. rosmarinus, linalool/linalyl acetate and carvone/limonene for M. &times; piperita and M. spicata, respectively. The chemotype of O. vulgare subsp. hirtum was identified as carvacrol. The optimization of harvesting time could lead to increased crop production and better EOs quality control, with numerous industrial benefits upon the commercial production of such products