In vitro studies indicate that miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is able to reach the CNS from the small intestine.
Miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is one of the flavonoids of St. John's wort (Hypericum perforatum L.) whose antidepressant activity has been shown by the forced swimming test, an in vivo pharmacological model with rats. However, nothing is known about its ability to reach the CNS after oral administration. We examined the pathway of miquelianin from the small intestine to the central nervous system using three in vitro membrane barrier cell systems. In the Caco-2 cell line, miquelianin showed a higher uptake (1.93 +/- 0.9 pmol x min(-1) x cm(-2)) than hyperoside (quercetin 3-O-beta-D-galactopyranoside; 0.55 +/- 0.18 pmol x min(-1) x cm(-2)) and quercitrin (quercetin 3-O-alpha-L-rhamnopyranoside; 0.22 +/- 0.08 pmol x min(-1) x cm(-2)). The permeability coefficient of miquelianin (Pc = 0.4 +/- 0.19 x 10(-6) cm/sec) was in the range of orally available drugs assuming sufficient absorption from the small intestine. Uptake and permeability of the examined compounds was increased by the MRP-2 inhibitor MK-571 indicating a backwards transport by this membrane protein. Porcine cell cultures of brain capillary endothelial cells were used as a model of the blood-brain barrier (bbb) and epithelial cells of the plexus chorioidei as a model of the blood-CSF barrier (bcb). Results indicate no active transport in one direction. Although moderate, the permeability coefficients (bbb: Pc = 1.34 +/- 0.05 x 10(-6) cm/sec; bcb: Pc = 2.0 +/- 0.33 x 10(-6) cm/sec) indicate the ability of miquelianin to cross both barriers to finally reach the CNS.
Juergenliemk
Guido
G
Institute of Pharmaceutical Biology and Phytochemistry, Westf, Wilhelms-University, Muenster, Germany. jurgenl@uni-muenster.de
Boje
Kerstin
K
Huewel
Sabine
S
Lohmann
Christina
C
Galla
Hans-Joachim
HJ
Nahrstedt
Adolf
A
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects; D018938:Caco-2 Cells / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D005960:Glucosides / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D020902:Hypericum; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects; D000089762:Multidrug Resistance-Associated Protein 2; D008517:Phytotherapy; D028321:Plant Preparations / Q000493:pharmacokinetics / Q000494:pharmacology*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013552:Swine
C000715087:ABCC2 protein, human; D005960:Glucosides; D000089762:Multidrug Resistance-Associated Protein 2; D028321:Plant Preparations; C012526:quercitrin; C021304:hyperoside; D011794:Quercetin; C110309:quercetin 3-O-glucopyranoside