Effects of nicotinic acetylcholine receptor-activating alkaloids on anxiety-like behavior in zebrafish.

Alkaloids are a structurally complex group of natural products that have a diverse range of biological activities and significant therapeutic applications. In this study, we examined the acute, anxiolytic-like effects of nicotinic acetylcholine receptor (nAChR)-activating alkaloids with reported neuropharmacological effects but whose effects on anxiety are less well understood. Because α4ß2 nAChRs can regulate anxiety, we first demonstrated the functional activities of alkaloids on these receptors in vitro. Their effects on anxiety-like behavior in zebrafish were then examined using the zebrafish novel tank test (NTT). The NTT is a relatively high-throughput behavioral paradigm that takes advantage of the natural tendency of fish to dive down when stressed or anxious. We report for the first time that cotinine, anatabine, and methylanatabine may suppress this anxiety-driven zebrafish behavior after a single 20-min treatment. Effective concentrations of these alkaloids were well above the concentrations naturally found in plants and the concentrations needed to induce anxiolytic-like effect by nicotine. These alkaloids showed good receptor interactions at the α4ß2 nAChR agonist site as demonstrated by in vitro binding and in silico docking model, although somewhat weaker than that for nicotine. Minimal or no significant effect of other compounds may have been due to low bioavailability of these compounds in the brain, which is supported by the in silico prediction of blood-brain barrier permeability. Taken together, our findings indicate that nicotine, although not risk-free, is the most potent anxiolytic-like alkaloid tested in this study, and other natural alkaloids may regulate anxiety as well.

Multi-residue contaminants and pollutants analysis in saffron spice by stir bar sorptive extraction and gas chromatography-ion trap tandem mass spectrometry.

A method for the simultaneous determination of 46 semi-volatile organic contaminants and pollutants in saffron has been developed for the first time using a stir bar sorptive extraction technique and thermal desorption in combination with gas chromatography-ion trap tandem mass spectrometry. The analytical method proposed was easy, rapid and sensitive and showed good linearity, accuracy, repeatability and reproducibility over the concentration range tested. Moreover, the correlation coefficients were higher than 0.98 for all target compounds and detection limits were lower than 1 microg/kg except for simazine. The present method was also applied for the analysis of trace contaminants in saffron samples.