Studying the Inhibitory Effect of Quercetin and Thymoquinone on Human Cytochrome P450 Enzyme Activities

Background: Quercetin (QR) and thymoquinone (TQ) are herbal remedies that are currently extensively used by the general population to prevent and treat various chronic conditions. Therefore, investigating the potential of pharmacokinetic interactions caused by the concomitant use of these herbal remedies and conventional medicine is warranted to ensure patient safety.

Purpose of the study: This study was conducted to determine the inhibitory effect of QR and TQ, two commonly used remedies, on the activities of selected Cytochrome P450 (CYP) Enzymes that play an important role in drug metabolism and/or toxicology.

Materials and methods: The in vitro studies were conducted using fluorescence-based high throughput assays using human c-DNA baculovirus expressed CYP Enzymes. For measuring CYP2E1 activity, a validated High-performance liquid chromatography (HPLC) assay was utilized to measure the formation of 6-hydroxychlorzoxazone.

Results: The obtained half-maximum inhibitory concentration values with known positive control inhibitors of this study were comparable to the published values indicating accurate experimental techniques. Although QR did not show any significant effect on CYP1A2 and CYP2E1, it exhibited a strong inhibitory effect against CYP2D6 and a moderate effect against CYP2C19 and CYP3A4. On the other hand, TQ demonstrated a strong and a moderate inhibitory effect against CYP3A4 and CYP2C19, respectively.

Conclusions: The findings of this study may indicate that consumption of QR or TQ, in the form of food or dietary supplements, with drugs that are metabolized by CYP2C19, CYP2D6, or CYP3A4 may cause significant herb-drug interactions.

Summary: Neither QR nor TQ has any significant inhibitory effect on the activity of CYP1A2 or CYP2E1 enzymesBoth QR and TQ have a moderate to strong inhibitory effect on CYP3A4 activityQR has a moderate inhibitory effect on CYP2C19 and a strong inhibitory effect on CYP2D6Both QR and TQ are moderate inhibitors of the CYP2C9 activity. Abbreviations used: ABT: Aminobenztriazole, BZF: 7,8 Benzoflavone, CYP: Cytochrome P450, GB: Gingko Biloba, IC₅₀: Half-maximum inhibitory concentration, KTZ: Ketoconazole, QND: Quinidine, QR: Quercetin, TCP: Tranylcypromine, TQ: Thymoquinone.

Cytochrome P450; half-maximum inhibitory concentration; herb-drug interactions; quercetin; thymoquinone.