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

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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.

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Acknowledgments

We would like to thank Department of Science and Technology, Government of India (Grant number: VI-D&P/372/10-11/TDT) for their financial assistance and support. One of the author Mr. T.M. Vijayakumar thank Mrs Kasthuri Bai. N and Mr. Vasanth. K from the ISISM Department for their support throughout the study.

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Authors and Affiliations

  1. Interdisciplinary School of Indian System of Medicine, SRM University, Kattankulathur, Kancheepuram (Dt), 603203, Tamil Nadu, India

    Thangavel Mahalingam Vijayakumar, Ramasamy Mohan Kumar & Kaliappan Ilango

  2. Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India

    Aruna Agrawal

  3. National Facility for Tribal and Herbal Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India

    Govind Prasad Dubey

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  1. Thangavel Mahalingam Vijayakumar
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  2. Ramasamy Mohan Kumar
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  3. Aruna Agrawal
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  4. Govind Prasad Dubey
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  5. Kaliappan Ilango
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Correspondence to Kaliappan Ilango.

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Vijayakumar, T.M., Kumar, R.M., Agrawal, A. et al. Comparative inhibitory potential of selected dietary bioactive polyphenols, phytosterols on CYP3A4 and CYP2D6 with fluorometric high-throughput screening. J Food Sci Technol 52, 4537–4543 (2015). https://doi.org/10.1007/s13197-014-1472-x

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  • DOI: https://doi.org/10.1007/s13197-014-1472-x

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