Abstract
The blood-brain barrier (BBB) permeability of twelve lignans and three phenolic malabaricones from the seeds of Myristica fragrans (nutmeg) were studied with the MDCK-pHaMDR cell monolayer model. The samples were measured by high-performance liquid chromatography and the apparent permeability coefficients (Papp) were calculated. Among the fifteen test compounds, benzonfuran-type, dibenzylbutane-type and arylnaphthalene-type lignans showed poor to moderate permeabilities with Papp values at 10−8–10−6 cm/s; those of 8-O-4′-neolignan and tetrahydrofuran-lignan were at 10−6–10−5 cm/s, meaning that their permeabilities are moderate to high; the permeabilities of malabaricones were poor as their Papp values were at 10−8–10−7 cm/s. To 5-methoxy-dehydrodiisoeugenol (2), erythro-2-(4-allyl-2,6-dimethoxyphenoxy)-1-(3,4-dimethoxyphenyl)-propan-1-ol acetate (6), verrucosin (8), and nectandrin B (9), an efflux way was involved and the main transporter for 6, 8 and 9 was demonstrated to be P-glycoprotein. The time and concentration dependency experiments indicated the main transport mechanism for neolignans dehydrodiisoeugenol (1), myrislignan (7) and 8 was passive diffusion. This study summarized the relationship between the BBB permeability and structure parameters of the test compounds, which could be used to preliminarily predict the transport of a compound through BBB. The results provide a significant molecular basis for better understanding the potential central nervous system effects of nutmeg.
Highlights
Blood-brain barrier (BBB) is a primary interface between the central nervous system (CNS)and the systemic circulation
The bidirectional transport studies of malabaricones and lignans were taken on this Madin–Darby Canine kidney (MDCK)-pHaMDR cell monolayer model
Have found that log D is the main determinant in the ability of diterpenes from Sideritis spp. across the BBB, and we demonstrate that, forfor lignans fromthe the seeds of Myristica fragrans, BBB,here and here we demonstrate that, lignansand andmalabaricones malabaricones from seeds of Myristica fragrans, log D log may have a great effect on the in vitro permeability across
Summary
Blood-brain barrier (BBB) is a primary interface between the central nervous system (CNS). The MDCK-pHaMDR cell model, established by Pastan et al in 1988, is MDCK cells transfected with human multidrug resistance (MDR1) gene [4] As it displays morphological (i.e., ultrastructurally defined tight junctions), enzymatic (acetylcholinesterase, butyrylcholinesterase, gamma-glutamyl transpeptidase, superoxide dismutase, alkaline phosphatase, lactate dehydrogenase), antigenic (i.e., Factor VIII) similarities with BBB as well as high expression of P-glycoprotein (P-gp), this cell model has been developed into a screening tool for drug transport in BBB [5,6,7]. The aim is to find out whether they can penetrate across the BBB, as well as the relationship between the structure and permeability
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