(+)-Chenabinol (Revised NMR Data) and Two New Alkaloids from Berberis vulgaris and their Biological Activity.

A known alkaloid (+)-chenabinol (1) and two new secobisbenzylisoquinoline alkaloids were isolated by standard chromatographic methods from the root bark of Berberis vulgaris L. The structures of the new alkaloids, named berkristine (2) and verfilline (3), were established by spectroscopic (including 2D NMR), and HRMS (ESI) methods. The alkaloids were tested for their inhibition activity of human cholinesterases and prolyl oligopeptidase. Compound 1 inhibited human butyrylcholinesterase with an IC50 value of 44.8 ± 5.4 µM.

Alkaloids from Peumus boldus and their acetylcholinesterase, butyrylcholinesterase and prolyl oligopeptidase inhibition activity.

Eleven isoquinoline alkaloids (1-11) were isolated from dried leaves of Peumus boldus Mol. by standard chromatographic methods. The chemical structures were elucidated by MS, and 1D and 2D NMR spectroscopic analysis, and by comparison with literature data. Compounds isolated in sufficient amount were evaluated for their acetylcholinesterase, and butyrylcholinesterase inhibition activity using Ellman's method. In the prolyl oligopeptidase assay, Z-Gly-Pro-p-nitroanilide was used as substrate. Promising butyrylcholinesterase inhibition activities were demonstrated by two benzylisoquinoline alkaloids, reticuline (8) and N-methylcoclaurine (9), with IC50 values of 33.6 ± 3.0 µM and 15.0 ± 1.4 µM, respectively. Important prolyl oligopeptidase inhibition activities were shown by N-methyllaurotetanine (6) and sinoacutine (4) with IC50 values of 135.4 ± 23.2 µM and 143.1 ± 25.4 µM, respectively. Other tested compounds were considered inactive.

Chemical composition of bioactive alkaloid extracts from some Narcissus species and varieties and their biological activity.

Alkaloid extracts of eight Narcissus (Amaryllidaceae) species and varieties were studied with respect to their acetylcholinesterase (HuAChE) and butyrylcholinesterase (HuBuChE) inhibitory activity and alkaloid patterns. Thirty alkaloids were determined by GC/MS, and twenty-five of them identified from their mass spectra, retention times and retention indexes. Promising HuAChE inhibition activity was demonstrated by six Narcissus taxa and HuBuChE inhibition by N. jonquila cv. Double Campernelle and N. nanus cv. Elka with IC50 values of 24.1 +/- 1.9 microg/mL and 25.1 +/- 1.8 microg/mL, respectively. Two alkaloids were isolated in pure form using preparative TLC and identified as the galanthamine type alkaloid narwedine and the lycorine type alkaloid incartine. Both compounds were tested for their biological activity. They were considered inactive in HuAChE/HuBuChE assays, but showed promising prolyl oligopeptidase inhibition activities with IC50 values of 0.95 +/- 0.12 mM and 0.91 g 0.09 mM, respectively.

Revised NMR data for 9-O-demethylgalanthine: an alkaloid from Zephyranthes robusta (Amaryllidaceae) and its biological activity.

Ongoing studies of Zephyranthes robusta resulted in the isolation of the lycorine-type alkaloid previously called carinatine and 10-O-demethylgalanthine. The NMR data given previously for this compound were revised and completed by two-dimensional 1H-1H and 1H-13C chemical shift correlation experiments. The name of the isolated compound was corrected to 9-O-demethylgalanthine in accordance with the currently used system of numbering of lycorine-type alkaloids. 9-O-Demethylgalanthine and galanthine, a previously isolated alkaloid from Z robusta, were inactive in acetylcholinesterase/butyrylcholinesterase assays (IC50 > 500 microM), but showed important prolyl oligopeptidase inhibition activity.

Berbanine: a new isoquinoline-isoquinolone alkaloid from Berberis vulgaris (Berberidaceae).

A new isoquinoline-isoquinolone alkaloid was isolated from the root bark of Berberis vulgaris and named berbanine. The structure was established by spectroscopic methods (including 2D NMR, HR-EI-MS).

Alkaloids from Chlidanthus fragrans and their acetylcholinesterase, butyrylcholinesterase and prolyl oligopeptidase activities.

Eleven Amaryllidaceae alkaloids (1-11) were isolated from fresh bulbs of Chlidanthus fragrans Herb. The chemical structures were elucidated by MS, and 1D and 2D NMR spectroscopic experiments. Complete NMR assignments were achieved for deoxypretazzetine (1). All compounds were evaluated for their erythrocytic acetylcholinesterase and serum butyrylcholinesterase inhibition activity using Ellman's method. In the prolyl oligopeptidase assay, Z-Gly-Pro-p-nitroanilide was used as substrate. In biological assays, only the crinine type Amaryllidaceae alkaloid undulatine showed promising acetylcholinesterase and prolyl oligopeptidase inhibition activity with IC50 values of 23.0 +/- 1.0 microM and 1.96 +/- 0.12 mM, respectively. Other isolated compounds were considered inactive.

Corylucinine, a new alkaloid from Corydalis cava (Fumariaceae), and its cholinesterase activity.

A new benzyldihydroisoquinoline alkaloid (1) was isolated from the tubers of Corydalis cava and named corylucinine. Additionally, 8-trichloromethyl-7,8-dihydropalmatine (2), an isolation artifact of tetrahydropalmatine, was obtained. The structures were established by spectroscopic (including 2D NMR and optical rotation) and HR-ESI-MS methods. Both compounds were tested for human blood acetylcholinesterase (HuAChE) and human plasma butyrylcholinesterase (HuBuChE) inhibitory activity. In comparison with the used standards, both compounds showed only moderate inhibitory activity against HuAChE (IC50,. HuAChE = 127.6 +/- 5.2 microM for 1, and IC50, HuAChE = 82.9 +/- 3.9 microM for 2) and none against HuBuChE.

Effect of vagal nerve stimulation on interictal epileptiform discharges: a scalp EEG study.

PURPOSE: To investigate the effects of acute vagal nerve stimulation (VNS) on interictal epileptiform discharges (IEDs). METHODS: Fifteen epilepsy patients, all of whom had been treated with VNS for > or =6 months, entered the study. In each subject, the absolute number of IEDs was counted at the baseline period (BP), the stimulation period (SP), six interstimulation periods (IPs), and the prestimulation period (PP), by using an original paradigm. The number of IEDs at the BP and the PP was compared with the number of IEDs at the SP and IPs. The results were correlated with other variables (the duration of VNS, the value of the output current, the duration of epilepsy, the type of epilepsy, the effect of VNS, and the effect of extrastimulation). RESULTS: We observed a significantly higher reduction in the number of IEDs in the SP and all the IPs as compared with the BP. We noticed a significantly higher reduction in the number of IEDs in the SP and in the first IP as compared with the PP. The reduction of IEDs was greater in patients who responded to VNS (>50% reduction of all seizures) and in patients who responded positively to magnetic extrastimulation. There were no other significant results in the reduction of IEDs when comparing other variables. CONCLUSIONS: Short-term VNS reduces IEDs significantly. The reduction is most prominent during the SP (i.e., when the pulse generator is active). The value of reduction of IEDs is higher in patients who respond to VNS and in patients with positive experiences with magnetic extrastimulation. These results can be useful in predicting the effect of VNS.