| MECHANISM OF ACTION |
The herbal product is known to promote the breakdown of a number of coadministered drugs, presumably by inducing liver enzymes that metabolize them (see page 45). Among these drugs are oral contraceptives and the immunosuppressant cyclosporin, which are metabolized by a cytochrome P450 oxyge nase dubbed CYP3A4. team reasoned that St. John's wort induces the expression of CYP3A4. Subsequently, they showed that extracts of the herbal product activate a steroid/thyroid hormone receptor that binds to the promoter for the CYP3A4 gene. And they identified hyperforin (shown) as the constituent that most potently activates the receptor. The findings illustrate the value of testing herbal remedies and drug candidates for their potential to elicit drug-drug interactions by increasing expression of the CYP3A4 gene, the team says
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