Effect of St. John's Wort extract on intestinal expression of cytochrome P4501A2: studies in LS180 cells.
OBJECTIVE
St. John's Wort (SJW) is known to induce expression and activity of cytochrome P4503A4 (CYP3A4). However, its effects on other cytochrome P450 (CYP) are not well understood. Our objective was to characterise the effect of SJW on the expression of CYP1A2 in the LS180 intestinal cell model.


METHODS
LS180 cells were cultured in the presence and absence of SJW extract for 48 hours. CYP1A2 protein content was measured by Western blot analysis using monoclonal antibody. Time-dependent expression of CYP1A2 was assessed during exposure to SJW extract for 24 hours and following its removal for another 24 hours.


RESULTS
SJW increased the expression of CYP1A2 in the LS180 cells in a concentration dependent manner. The induction was time-dependent, as enzyme levels returned to baseline within 4-8 hours after removal of SJW.


CONCLUSIONS
SJW reversibly induces expression of CYP1A2 in LS180 cells. This induction may be responsible for reduced plasma theophylline concentrations upon co-administration of SJW, as reported earlier.
Karyekar
C S
CS
Pharmacokinetics-Biopharmaceutics Laboratory, School of Pharmacy, University of Maryland, Baltimore 21201, USA.
Eddington
N D
ND
Dowling
T C
TC
D015153:Blotting, Western; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000187:drug effects*; D004347:Drug Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013997:Time Factors; D014407:Tumor Cells, Cultured
D010936:Plant Extracts; D019388:Cytochrome P-450 CYP1A2