The acylated phloroglucinol, hyperforin, the main active ingredient of St. John’s Wort, exerts antidepressant properties via indirect inhibition of serotonin reuptake by selectively activating the canonical transient receptor potential channel 6 (TRPC6). Hyperforin treatment can lead to drug–drug interactions due to potent activation of the nuclear receptor PXR (NR1I2), a key transcriptional re...

The acylated phloroglucinol, hyperforin, the main active ingredient of St. John's Wort, exerts antidepressant properties via indirect inhibition of serotonin reuptake by selectively activating the canonical transient receptor potential channel 6 (TRPC6). Hyperforin treatment can lead to drug-drug interactions due to potent activation of the nuclear receptor PXR (NR1I2), a key transcriptional re...

the activity of cytochrome p450 isozyme 3a4 (cyp3a4) enzyme and p-glycoprotein (p-gp) is modulated by grapefruit juice and herbal drugs. cyp3a4 is the major phase i drug metabolizing enzyme and p-gp is an atp-dependent drug efflux pump that regulates the intestinal absorption of orally administered drugs. honey is commonly consumed as a dietary supplement. however, its influence on human cyp3a4...

We report a novel approach to study allostery which combines the use of carefully selected bioconjugates and hydrogen–deuterium exchange mass spectrometry (HDX-MS). This strategy avoids issues related weak substrate binding ligand relocalization. The utility our method is demonstrated using human cytochrome P450 3A4 (CYP3A4), most important drug-metabolizing enzyme. Allosteric activation inhibi...

PURPOSE In recent years, a number of natural medicines have been reported to have inductive or inhibitive effects on the activity of drug metabolizing enzymes, upon co-administration with prescribed medicines. However, information regarding natural medicine-drug interactions that influence drug metabolism is limited owing to the lack of efficient screening method for such interactions. Therefor...

Aim Human cytochrome P450 3A4 is the most abundant isoform of P450 enzyme in the liver. It plays an important role in the metabolism of wide variety of xenobiotic and endogenous substrates. So far, there are few reports about the functional characterization of CYP3A4 variants in terms of specific substrates. The aim of this study was to systematically investigate the genetic polymorphisms of 23...

objective: to evaluate the effect of niprd-am1 on cyp3a4 in order to generate clinically significant data for its safe and efficacious use. materials and methods: niprd-am1 is a phytomedicine developed from aqueous root extracts of nauclea latifolia smith (rubiaceae) for the treatment of uncomplicated malaria. the effect of niprd-am1 on cyp3a4 was measured with and without the addition of niprd...

CYP3A4 is a key enzyme involved in the metabolism of numerous compounds, such as paclitaxel, and its activity shows an extensive inter-individual variation which can influence treatment response. The study's purpose was to investigate the potential predictive role of a CYP3A4 profile (CYP3A4*1B, rs2740574 and CYP3A4*22, rs35599367) in serous ovarian cancer patients treated with first-line chemo...

Activities of testosterone, nifedipine, and midazolam oxidation by recombinant cytochrome P-450 (P-450) 3A4 coexpressed with human NADPH-P-450 reductase (NPR) in bacterial membranes (CYP3A4/NPR membranes) were determined in comparison with those of other recombinant systems and of human liver microsomes with high contents of CYP3A4. Growth conditions for Escherichia coli transformed with the bi...

CYP3A4 is the most abundant isoform of cytochrome P450 (CYP) in adult human liver. It metabolizes numerous clinically, physiologically, and toxicologically important compounds. The expression of CYP3A4 varies 40-fold in individual human livers, and metabolism of CYP3A4 substrates varies at least 10-fold in vivo. Single nucleotide polymorphisms (SNPs) in CYP3A4 were identified by direct sequenci...