title: 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, IC50 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.
authors.affiliation: Interdisciplinary School of Indian System of Medicine, SRM University, Kattankulathur, Kancheepuram (Dt), 603203 Tamil Nadu India.
authors.forename: Thangavel Mahalingam
authors.initials: TM
authors.lastname: Vijayakumar
authors.affiliation: Interdisciplinary School of Indian System of Medicine, SRM University, Kattankulathur, Kancheepuram (Dt), 603203 Tamil Nadu India.
authors.forename: Ramasamy Mohan
authors.initials: RM
authors.lastname: Kumar
authors.affiliation: Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 Uttar Pradesh India.
authors.forename: Aruna
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: National Facility for Tribal and Herbal Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 Uttar Pradesh India.
authors.forename: Govind Prasad
authors.initials: GP
authors.lastname: Dubey
authors.affiliation: Interdisciplinary School of Indian System of Medicine, SRM University, Kattankulathur, Kancheepuram (Dt), 603203 Tamil Nadu India.
authors.forename: Kaliappan
authors.initials: K
authors.lastname: Ilango
keywords: CYP3A4 & CYP2D6; CYP450-CO complex assay; Cytochrome P450; Food-drug interaction; Interaction potential