Planta Med 2003; 69(11): 1013-1017
DOI: 10.1055/s-2003-45148
Original Paper
Biochemistry and Molecular Biology
© Georg Thieme Verlag Stuttgart · New York

In Vitro Studies Indicate that Miquelianin (Quercetin 3-O-ß-D-Glucuronopyranoside) is Able to Reach the CNS from the Small Intestine

Guido Juergenliemk1 , Kerstin Boje1 , Sabine Huewel2 , Christina Lohmann2 , Hans-Joachim Galla2 , Adolf Nahrstedt1
  • 1Institute of Pharmaceutical Biology and Phytochemistry; Westf. Wilhelms-University, Muenster, Germany
  • 2Institute of Biochemistry; Westf. Wilhelms-University, Muenster, Germany
Weitere Informationen

Publikationsverlauf

Received: April 24, 2003

Accepted: August 14, 2003

Publikationsdatum:
09. Januar 2004 (online)

Abstract

Miquelianin (quercetin 3-O-ß-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 × min-1 × cm-2) than hyperoside (quercetin 3-O-ß-D-galactopyranoside; 0.55 ± 0.18 pmol × min-1 × cm-2) and quercitrin (quercetin 3-O-α-L-rhamnopyranoside; 0.22 ± 0.08 pmol × min-1 × cm-2). The permeability coefficient of miquelianin (P c = 0.4 ± 0.19 × 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: P c = 1.34 ± 0.05 × 10 - 6 cm/sec; bcb: P c = 2.0 ± 0.33 × 10 - 6 cm/sec) indicate the ability of miquelianin to cross both barriers to finally reach the CNS.

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Dr. Guido Juergenliemk

Institute of Pharmaceutical Biology and Phytochemistry

Westf. Wilhelms-University

Hittorfstr. 56

49149 Muenster

Germany

Telefon: +49-251-833-3376

Fax: +49-251-833-8341

eMail: jurgenl@uni-muenster.de