Interactions between CYP3A4 and Dietary Polyphenols

Abstract

The human cytochrome P450 enzymes (P450s) catalyze oxidative reactions of a broad spectrum of substrates and play a critical role in the metabolism of xenobiotics, such as drugs and dietary compounds. CYP3A4 is known to be the main enzyme involved in the metabolism of drugs and most other xenobiotics. Dietary compounds, of which polyphenolics are the most studied, have been shown to interact with CYP3A4 and alter its expression and activity. Traditionally, the liver was considered the prime site of CYP3A-mediated first-pass metabolic extraction, but in vitro and in vivo studies now suggest that the small intestine can be of equal or even greater importance for the metabolism of polyphenolics and drugs. Recent studies have pointed to the role of gut microbiota in the metabolic fate of polyphenolics in human, suggesting their involvement in the complex interactions between dietary polyphenols and CYP3A4. Last but not least, all the above suggests that coadministration of drugs and foods that are rich in polyphenols is expected to stimulate undesirable clinical consequences. This review focuses on interactions between dietary polyphenols and CYP3A4 as they relate to structural considerations, food-drug interactions, and potential negative consequences of interactions between CYP3A4 and polyphenols.

Management of Benign Prostatic Hyperplasia: Could Dietary Polyphenols Be an Alternative to Existing Therapies?

“…Amongst the CYP enzymes which are responsible for the metabolism of a wide array of endogenous substances, (example-steroids, hormones, lipids, and bile acids), xenobiotics (example-drugs and pollutants from the environment), and dietary products and/dietary polyphenols, CYP 3A4 has been shown to be the major enzyme that is involved in the metabolism of drugs and xenobiotics in the liver and gut (Loai and Zohar, 2015). It has also been shown to be expressed in the prostate, breast, gut, colon, small intestine, and the brain (Ferguson and Tyndale, 2011; Loai and Zohar, 2015).…”

“…It has also been shown to be expressed in the prostate, breast, gut, colon, small intestine, and the brain (Ferguson and Tyndale, 2011; Loai and Zohar, 2015). …”

Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation

“…Despite being a potent phytomolecule, the use of Mgf is restricted due to its low and variable oral bioavailability (about 1.5 to 5.0%), usually ascribed to its poor aqueous solubility (0.1 to 0.3 mg/mL), low lipophilicity, high P-gp efflux, considerable first-pass metabolism and cytochrome P-450 mediated metabolism in gut enterocytes (Basheer and Kerem, 2015;Khurana et al, 2016). Besides, Mgf display rapid clearance from the body via glucuronidation of the hydroxyl groups present at position-6 and 7 of its xanthone moiety, which, in turn, tends to reduce its potential antioxidant and anticancer activities, due to shorter half-life (van der Merwe et al, 2011).…”

Biodisponibilidad de compuestos fenólicos dietéticos: Revisión

“…It has been reported that CYP3A4 interacts with dietary phenolic compounds. This suggests that coadministration of drugs and phenolic compounds may stimulate some toxicity consequences 38 .…”

“…The metabolic action of CYP450 on phenolic compounds depends largely on their functional groups, molecular weight, stereostructure, glycosylation, polymerization, and conjugation with other phenolic compounds 38,39 . Moreover, flavonoids rich in hydroxylic groups are less likely to be metabolized by CYP450; paradoxically, tea catechins (flavonoids rich in hydroxyl groups) are reported to inhibit CYP450 40 .…”