Browsing by Author "Ramasamy Mohan Kumar"

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Comparative inhibitory potential of selected dietary bioactive polyphenols, phytosterols on CYP3A4 and CYP2D6 with fluorometric high-throughput screening
(Springer, 2015) Thangavel Mahalingam Vijayakumar; Ramasamy Mohan Kumar; Aruna Agrawal; Govind Prasad Dubey; Kaliappan Ilango
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. © 2014, Association of Food Scientists & Technologists (India).
Effect of Dioscorea bulbifera and its Major Bioactive Compound, Diosgenin on CYP450 Mediated Drug Metabolism
(Taylor and Francis Ltd., 2015) Thangavel Mahalingam Vijayakumar; Kaliappan Ilango; Ramasamy Mohan Kumar; Aruna Agrawal; Govind Prasad Dubey
Cytochrome P450 (CYP450) inhibition by the bioactive molecules of herbs leading to greater potential for toxicity of co-administered drugs. Diosgenin is an important bioactive steroidal sapogenin from Dioscorea bulbifera belonging to the triterpene group and is of great interest to the pharmaceutical industry. The purpose of this study was, to find whether D. bulbifera and Diosgenin influences the effect on rat CYP450 enzymes and its important isoforms (CYP3A4, CYP2D6) by using high through put screening. CYP450-CO Complex assay was performed in rat pooled liver microsomes to calculate percentage inhibition of test samples on CYP450. IC values were determined by fluorometric assays of CYP3A4 and CYP2D6. Mode of inhibition of Diosgenin on these CYPs were further assessed by molecular docking studies with the Glide (Schrodinger Inc. U.S.A.). In CYP450 inhibition assay, the inhibitory potential of herb extract (40.44±1.28 %) was found to be less than positive control (72.08±1.96 %). In fluorometric assay, herb extract exhibited higher IC values (96.21 ± 1.32 to 180.42±0.12 µg/ml) when compared to positive inhibitors and lower than Diosgenin (172.54±0.52 to 201.86±1.49 µg/ml) on CYP3A4 and CYP2D6. Based on the inhibitory potential, test substances exhibited very less interaction capacity, thereby leading to less significant herb-drug interaction with co-administered drugs.Further clinical studies are required to fully assess the safety of Diosgenin in terms of CYP450. © 2015, © 2015 Har Krishan Bhalla & Sons.