Functional induction and de-induction of P-glycoprotein by St. John's wort and its ingredients in a human colon adenocarcinoma cell line

Run Tian, Noriko Koyabu, Satoshi Morimoto, Yukihiro Shoyama, Hisakazu Ohtani, Yasufumi Sawada

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Continuous use of St. John's wort decreases the bioavailabilities of a variety of drugs. This interaction is attributed to the induction of cytochrome P450 3A4 and/or P-glycoprotein. In this study, we aimed to examine the chronic effects of St. John's wort and its constituents, hyperforin and hypericin, on the expression and function of P-glycoprotein in an intestinal cell line, LS 180. We also examined the acute inhibitory effect of St. John's wort on P-glycoprotein by using LLC-GA5-COL150 cells, which overexpress P-glycoprotein. St. John's wort and hyperforin but not hypericin increased the expression of P-glycoprotein in LS 180 cells. Removal of St John's wort resulted in a restoration of P-glycoprotein level within 48 h. The content of hyperforin in St. John's wort extract was high enough to induce P-glycoprotein, suggesting that the induction of P-glycoprotein by St. John's wort can be almost attributable to hyperforin. The LS 180 cells chronically exposed to St. John's wort or hyperforin exhibited the increase in the function of P-glycoprotein assessed by the efflux of digoxin, and the activities correlated well with P-glycoprotein level. On the other hand, St. John's wort and its two constituents did not show any acute effect on P-glycoprotein-mediated transport of digoxin. St John's wort induced P-glycoprotein in vitro that functions as a drug efflux pump. Hyperforin is considered to be a primary cause of the inductive effect of St. John's wort. Long-term administration of St. John's wort may cause clinically significant decrease in the plasma concentrations of P-glycoprotein substrates.

Original languageEnglish
Pages (from-to)547-554
Number of pages8
JournalDrug Metabolism and Disposition
Volume33
Issue number4
DOIs
Publication statusPublished - 2005 Apr
Externally publishedYes

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Hypericum
P-Glycoprotein
Colon
Adenocarcinoma
Cells
Cell Line
Digoxin
Cytochrome P-450 CYP3A
Pharmaceutical Preparations
Biological Availability
Restoration
hyperforin

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Functional induction and de-induction of P-glycoprotein by St. John's wort and its ingredients in a human colon adenocarcinoma cell line. / Tian, Run; Koyabu, Noriko; Morimoto, Satoshi; Shoyama, Yukihiro; Ohtani, Hisakazu; Sawada, Yasufumi.

In: Drug Metabolism and Disposition, Vol. 33, No. 4, 04.2005, p. 547-554.

Research output: Contribution to journalArticle

Tian, Run ; Koyabu, Noriko ; Morimoto, Satoshi ; Shoyama, Yukihiro ; Ohtani, Hisakazu ; Sawada, Yasufumi. / Functional induction and de-induction of P-glycoprotein by St. John's wort and its ingredients in a human colon adenocarcinoma cell line. In: Drug Metabolism and Disposition. 2005 ; Vol. 33, No. 4. pp. 547-554.
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