St John's wort induces both cytochrome P450 3A4–catalyzed sulfoxidation and 2C19–dependent hydroxylation of omeprazole

2004 ◽  
Vol 75 (3) ◽  
pp. 191-197 ◽  
Author(s):  
L Wang
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 3A4 ◽  
St John’S Wort ◽  
St John's Wort

Effect of St. John’s Wort on Drug Metabolism by Induction of Cytochrome P450 3A4 Enzyme

2004 ◽  
Vol 59 (5) ◽  
pp. 358-359 ◽  
Author(s):  
John S. Markowitz ◽  
Jennifer L. Donovan ◽  
C. Lindsay DeVane ◽  
Robin M. Taylor ◽  
Ying Ruan ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Cytochrome P450 3A4 ◽  
St John’S Wort ◽  
St John's Wort

scholarly journals THE EFFECT OF ST JOHN'S WORT (HYPERICUM PERFORATUM) ON CYTOCHROME P450 1A2 ACTIVITY IN PERFUSED RAT LIVER

2011 ◽  
Vol 155 (3) ◽  
pp. 253-257 ◽  
Author(s):  
Miroslav Dostalek ◽  
Jana Pistovcakova ◽  
Jan Jurica ◽  
Alexandra Sulcova ◽  
Josef Tomandl
Keyword(s):  
Cytochrome P450 ◽  
Rat Liver ◽  
Hypericum Perforatum ◽  
Perfused Rat Liver ◽  
Cytochrome P450 1A2 ◽  
St John’S Wort ◽  
St John's Wort

scholarly journals No Clinically Relevant Interactions of St. John's Wort Extract Ze 117 Low in Hyperforin With Cytochrome P450 Enzymes and P‐glycoprotein

2019 ◽  
Vol 106 (2) ◽  
pp. 432-440 ◽  
Author(s):  
Catherine Zahner ◽  
Esther Kruttschnitt ◽  
Julia Uricher ◽  
Michael Lissy ◽  
Martin Hirsch ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzymes ◽  
St John’S Wort ◽  
St John's Wort ◽  
P Glycoprotein

scholarly journals St John's wort, a herbal antidepressant, activates the steroid X receptor

2000 ◽  
Vol 166 (3) ◽  
pp. R11-R16 ◽  
Author(s):  
JM Wentworth ◽  
M Agostini ◽  
J Love ◽  
JW Schwabe ◽  
VK Chatterjee
Keyword(s):  
Cytochrome P450 ◽  
Orphan Nuclear Receptor ◽  
Transactivation Domain ◽  
Cytochrome P450 3A ◽  
Binding Studies ◽  
P450 Gene ◽  
Steroid Receptor Coactivator ◽  
St John’S Wort ◽  
St John's Wort ◽  
Key Residues

St John's wort (SJW), an extract of the medicinal plant Hypericum perforatum, is widely used as a herbal antidepressant. Recently, this agent has been found to adversely affect the metabolism of various coadministered drugs. Steroid X receptor (SXR), an orphan nuclear receptor, induces hepatic cytochrome P450 gene expression in response to diverse endogenous steroids, xenobiotics and drugs. Here, we report that, when coexpressed with SXR, a reporter construct derived from the cytochrome P450 3A promoter is activated by St John's wort. A GAL4-SXR ligand binding domain (LBD) fusion mediates concentration-dependent transactivation by SJW, whereas a mutant GAL4-SXR fusion, containing substitutions in key residues in a transactivation domain, is inactive. SJW recruits steroid receptor coactivator-1 to SXR in a two-hybrid assay and competes with radiolabelled ligand in binding studies, suggesting it interacts directly with the receptor LBD. Of two constituents of SJW, we find that hyperforin, but not hypericin, mediates both transactivation and coactivator recruitment by SXR. Our observations suggest that SXR activation by St John's wort mediates its adverse interaction with drugs metabolised via the CYP 3A pathway. Future development of SJW derivatives lacking SXR activation, may enable its antidepressant and drug-metabolising properties to be dissociated.

scholarly journals Induction of Cytochrome P450 CYP3A by St John's Wort in the Rat Liver and Intestine

2007 ◽  
Vol 2 ◽  
pp. 117863370700200 ◽  
Author(s):  
Thuong Tran Phan ◽  
See Huey Heng ◽  
Damien Abarno ◽  
Ross Allan McKinnon ◽  
Suong Ngoc Thi Ngo
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Molecular Mechanism ◽  
Fold Increase ◽  
The Body ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Cyp3a Activity ◽  
St John’S Wort ◽  
St John's Wort

It has been well reported that complementary medicines can significantly alter the way the body handles conventional drugs, leading to potential fatal herb-drug interactions. The aim of the present study was to investigate the molecular mechanism of drug interactions involving St John's wort (SJW) (Hypericum perforatum L), a popular herbal medicine widely used for depression, particularly examining changes in the expression of cytochrome P450 CYP3A, the most abundant drug metabolising CYP enzymes in man. Eighteen Sprague-Dawley (SD) rats were assigned randomly into 3 groups (n = 6/group): control, low dose and high dose (500 and 1000 mg/kg/day of SJW, equal to 1500 and 3000 µg/kg/day of Hypericin). Each group was treated with SJW or control preparation, by gastric gavage, for 14 consecutive days. Liver and intestinal CYP3A activity and protein and mRNA levels, from five segments of the intestine, were examined using CYP3A-dependent erythromycin N-demethylation activity assay, quantitative immuno-blotting and real-time RT-PCR. Increase in CYP3A activity and protein level by SJW was observed in some intestinal regions, with a 3.0 fold increase in liver CYP3A activity and a 10.6 fold increase in liver CYP3A1 mRNA (p < 0.05) in a dose dependent manner. The results suggested that up regulation of liver CYP3A mRNA and differential induction of intestinal CYP3A play an important role in the molecular mechanism of herb-drug interactions.

In VitroActivity of St. John's Wort Against Cytochrome P450 Isozymes and P-Glycoprotein

2004 ◽  
Vol 42 (2) ◽  
pp. 159-169 ◽  
Author(s):  
B.C. Foster ◽  
E.R. Sockovie ◽  
S. Vandenhoek ◽  
N. Bellefeuille ◽  
C.E. Drouin ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
St John’S Wort ◽  
St John's Wort ◽  
P Glycoprotein ◽  
P450 Isozymes ◽  
Cytochrome P450 Isozymes
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