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

Abstract

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 substitutio..