Planta Med 2006; 72(8): 685-690
DOI: 10.1055/s-2006-931585
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Hypericum perforatum: Which Constituents may Induce Intestinal MDR1 and CYP3A4 mRNA Expression?

Heike Gutmann1 , Birk Poller1 , Karin Berger Büter2 , Arabelle Pfrunder1 , Willi Schaffner2 , Jürgen Drewe1
  • 1Department of Clinical Pharmacology & Toxicology; University Clinic Basel, Basel, Switzerland
  • 2Institute of Pharmaceutical Biology, University of Basel, Witterswil, Switzerland
Further Information

Publication History

Received: May 31, 2005

Accepted: February 17, 2006

Publication Date:
01 June 2006 (online)

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Abstract

In vitro and in vivo studies suggest that extracts of St John’s wort (Hypericum perforatum, L.; SJWE) interact with various drugs, by enhancing their elimination, due to induction of intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp), the gene product of multidrug resistance gene 1 (MDR1/ABCB1). The aim of our study was to identify the major constituents responsible for this induction and their relative importance. Therefore, plant extracts were investigated that vary in these constituents with respect to their effect on mRNA expression of MDR1/CYP3A4. First, different pure constituents of Hypericum perforatum L. were investigated. Secondly, diverse SJWE with different concentrations of hyperforin, quercitrin and hypericin were investigated. The concentrations of hyperforin, hypericin, and quercitrin in the plant extracts were determined by HPLC, and an ”artificial extract” containing the same mixture of these constituents was investigated. Different plant extracts, pure constituents or ”artificial extracts” were applied to the human colon carcinoma-derived cell line (LS180) and the induction of MDR1 and CYP3A4 expression was analyzed by quantitative RT-PCR. MDR1 and CYP3A4 mRNA expression were both induced by single constituents of SJW such as hypericin and hyperforin in a concentration of 10 μM. Additionally, CYP3A4 mRNA expression was induced by quercitrin. SJW extracts containing hyperforin induced significantly MDR1 mRNA expression, whereas no CYP3A4 induction was observed after treatment with any of the investigated SJWE. These effects could be mimicked by ”artificial extracts” containing the same compositions of hyperforin, hypericin and quercitrin as the plant extracts.

References

Jürgen Drewe MD, MSc

Department of Clinical Pharmacology and Toxicology

University Clinic Basel

Petersgraben 4

4031 Basel

Switzerland

Phone: +41-61-265-3848

Fax: +41-61-265-8581

Email: juergen.drewe@unibas.ch