Modulation of P-glycoprotein function by St John's wort extract and its major constituents.
BACKGROUND
Recent data suggest some relevant drug interactions caused by St John's wort extract, which can be explained by interactions with the Cytochrome P450 system or P-Glycoprotein (Pgp). Interaction with Pgp, including activation, inhibition and induction, can lead to altered plasma or brain levels of Pgp substrates. The aim of the present study was to investigate the possible interactions of St John's wort extract and most relevant constituents with the transport activity of Pgp.


METHODS
We characterized the modulatory potencies in two in vitro assays using calcein-AM, first in VLB cells (a human lymphocytic leukemia cell line expressing Pgp) and second in PBCEC cells (porcine brain capillary endothelial cells).


RESULTS
The extract, as well as some of the tested constituents modulate the transport by Pgp in the micromolecular range. Quercetin and hyperforin seem to be most potent.


CONCLUSIONS
These findings suggest the possibility of drug interactions at the level of the gastro-intestinal absorption of drugs. Plasma levels of the constituents of St John's wort are very likely too low to interfere with Pgp at the blood-brain-barrier with the possible exception of quercetin.
Weber
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CC
Department of Pharmacology, Biocenter, University of Frankfurt, Marie-Curie-Strasse 9, 60439 Frankfurt, Germany.
Kressmann
S
S
Fricker
G
G
Müller
W E
WE
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain / Q000166:cytology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D042783:Endothelial Cells / Q000187:drug effects*; D005452:Fluoresceins / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology; D041743:Herb-Drug Interactions; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D007938:Leukemia; D008954:Models, Biological; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology; D013552:Swine; D013729:Terpenes / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000928:Antidepressive Agents; D001643:Bridged Bicyclo Compounds; D005452:Fluoresceins; D010936:Plant Extracts; D013729:Terpenes; D005473:Fluoxetine; C085925:calcein AM; D000639:Amitriptyline; D000255:Adenosine Triphosphate; D011794:Quercetin; D010696:Phloroglucinol; C001654:hyperforin