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DOI: 10.1055/s-0033-1352398
In vitro absorption studies of saffron ingredients (tr-Crocin-1, tr-Crocetin) in the Caco-2 and blood-brain barrier model
Saffron shows various effects on the central nervous system, e.g. improvement of long-term potentiation of learning and pronounced antidepressant properties, probably caused by NMDA-receptor activity and inhibition of glutamatergic synaptic transmission. Pharmacological effects have been investigated by in vitro, ex vivo and in vivo experiments, antidepressant properties were also confirmed by preliminary clinical trials. The pharmacological potential of this drug has been well studied but there is a lack of pharmacokinetic data.
Since the main compounds of hydroethanolic saffron extracts are Crocins, glycosylated C-20 carotenoids, we decided to investigate the absorption properties by in vitro experiments with Crocin-1 and the aglycon Crocetin. Investigations were carried out on Caco-2 cell line, representing the intestinal barrier and on two other in vitro models representing the blood-brain barrier. The aim of the following study was to show intestinal permeation characteristics of Crocin-1 and Crocetin by Caco-2 cells and to demonstrate central nervous system availability of Crocetin by different blood-brain barrier models.
The Caco-2 system was validated by quality assurance parameters as permeability of transport markers, transepithelial electrical resistance, and laser scanning microscopy. Permeation studies indicates that Crocin-1 was poorly absorbed (Papp= 2,33 *10-7 cm/s). In contrast high permeation rates were found for the aglycon Crocetin (Papp= 2,65 *10-5 cm/s).
Availability of Crocetin in the central nervous system was deduced from findings of permeation through in vitro models of blood brain barrier (Papp= 1,48 *10-6 cm/s) and blood cerebrospinal barrier (Papp= 3,75 *10-6 cm/s).
Based on these data it can be assumed that the glycosylated crocines are not bioavailable after oral administration, but after intestinal deglycosylation the aglycon Crocetin should be absorbed to the systemic compartment and should also permeate the blood-brain barrier.