Effect of Dioscorea bulbifera and its Major Bioactive Compound, Diosgenin on CYP450 Mediated Drug Metabolism

Abstract

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.