Comparative inhibitory potential of selected dietary bioactive polyphenols, phytosterols on CYP3A4 and CYP2D6 with fluorometric high-throughput screening

Abstract

Cytochrome P450 (CYP450) inhibition by the bioactive molecules of dietary supplements or herbal products leading to greater potential for toxicity of co-administered drugs. The present study was aimed to compare the inhibitory potential of selected common dietary bioactive molecules (Gallic acid, Ellagic acid, β-Sitosterol, Stigmasterol, Quercetin and Rutin) on CYP3A4 and CYP2D6 to assess safety through its inhibitory potency and to predict interaction potential with co-administered drugs. CYP450-CO complex assay was carried out for all the selected dietary bioactive molecules in isolated rat microsomes. CYP450 concentration of the rat liver microsome was found to be 0.474 nmol/mg protein, quercetin in DMSO has shown maximum inhibition on CYP450 (51.02±1.24 %) but less when compared with positive control (79.02±1.61 %). In high throughput fluorometric assay, IC 50 value of quercetin (49.08±1.02-54.36± 0.85 μg/ml) and gallic acid (78.46±1.32-83.84±1.06 μg/ml) was lower than other bioactive compounds on CYP3A4 and CYP2D6 respectively but it was higher than positive controls (06.28±1.76-07.74±1.32 μg/ml). In comparison of in vitro inhibitory potential on CYP3A4 and CYP2D6, consumption of food or herbal or dietary supplements containing quercetin and gallic acid without any limitation should be carefully considered when narrow therapeutic drugs are administered together.

Inhibitory Interactions of Aspalathus linearis (Rooibos) Extracts and Compounds, Aspalathin and Z-2-(β-d-Glucopyranosyloxy)-3-phenylpropenoic Acid, on Cytochromes Metabolizing Hypoglycemic and Hypolipidemic Drugs

“…Luteolin, the aglycone of rooibos flavone glucosides, orientin and isoorientin, and quercetin, the aglycone of rooibos flavonol glycosides, quercetin-3- O -robinobioside, rutin, hyperoside, and isoquercitrin, have previously been shown to inhibit CYP3A4 [46,47,48,49]. Quercetin is a more effective inhibitor of CYP3A4 than its 3- O -rutinoside, rutin [50]. The inhibition of CYP3A4 was also demonstrated to be both dose- and time-dependent.…”

Desensitizing Mitochondrial Permeability Transition by ERK-Cyclophilin D Axis Contributes to the Neuroprotective Effect of Gallic Acid against Cerebral Ischemia/Reperfusion Injury

“…Several studies have revealed that GA weakly and time-dependently inactivated CYP3A4 via its oxidative products, leading to more potential for toxicity of co-administered drugs (Stupans et al, 2002; Pu et al, 2015; Vijayakumar et al, 2015). Of note, CYP3A4 plays a key role in metabolic clearance of Nifedipine and Amlodipine in humans, which were commonly prescribed calcium channel blocker for the treatment of hypertension (Zhu et al, 2014; Wang X.F.…”

Diet, Gut Microbiota, and Vitamins D + A in Multiple Sclerosis

“…They show anti-inflammatory, antiangiogenic, and antiviral properties, and upregulate the catabolism [13,78]. An important aspect of polyphenols is that they can inhibit some cytochrome P450 enzymes (CYPs) and therefore they may interfere with drugs [79]. It has been found that the anti-inflammatory effect of polyphenols in vitro may depend on their chemical structure [80]; thus, a mixture of flavonoids and nonflavonoids may be more effective than supplementation with only 1 type of polyphenols [81].…”