St. John's Wort (Hypericum perforatum) induces overexpression of multidrug resistance protein 2 (MRP2) in rats: a 30-day ingestion study.
St. John's Wort (Hypericum perforatum, SJW) has been used as a herbal medicine for the treatment of depression in oral doses of 900-1050 mg/day in humans. However, the ingestion of SJW was reported to cause interactions with drugs. In the present study, we examined the effects of SJW treatment on the induction of drug transporters and enzymes in rats. An immunoblot analysis was performed to quantify the expression of the transporters and enzymes. SJW was given at a dose of 400 mg/kg/day, since it was reported that 400 mg/kg/day is antidepressant effective dose in rats. When SJW was administered for 10 days, the amounts of multidrug resistance protein 2 (MRP2), glutathione S-transferase-P (GST-P) and cytochrome P450 1A2 (CYP1A2) in the liver were increased to 304%, 252% and 357% of controls, respectively, although the amounts of P-glycoprotein and multidrug resistance protein 1 were not changed. Under the same conditions, an increase of MRP2 in the kidney was not observed. The increase in the levels of each protein was maximal at 10 days after SJW treatment and lasted for at least 30 consecutive days. These results suggest that SJW induces hepatic MRP2, GST-P and CYP1A2 overexpressions, and thus, it could affect drug metabolism, conjugation and disposition.
Shibayama
Y
Y
Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Ikeda
R
R
Motoya
T
T
Yamada
K
K
D018528:ATP-Binding Cassette Transporters; D000284:Administration, Oral; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects*; D005982:Glutathione Transferase / Q000096:biosynthesis*; D020902:Hypericum / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D002352:Carrier Proteins; D010936:Plant Extracts; D019388:Cytochrome P-450 CYP1A2; D005982:Glutathione Transferase