Inhibitory effect of phyllanthus emblica aqueous extract on recombinant human cytochrome P450

Abstract

Phyllanthus emblica Linn. is a plant in family Euphorbiaceae. Several parts of P. emblica are used for antitussive, anti-inflammatory and antipyretic. Its fruits are the rich source of ascorbic acid. From the past to present, investigations regarding pharmacological effects of P. emblica are still ongoing. The aim of this study is to investigate the inhibitory effect of P. emblica aqueous extract on recombinant human cytochrome P450 such as CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 in vitro study. IC50 of the extract on each CYP isoform was determined. The mechanism-based inhibition was investigated using the IC50 ratio. Then, the type of reversible inhibition was investigated using Lineweaver-Burk plot for determining Ki value, the inhibition constant for predicting of herb-drug interaction. The result showed that the extract exhibited inhibitory effects on CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 with IC50 ± SE of 310.27 ± 5.07, 194.72 ± 2.94, 589.52 ± 14.32, 310.27 ± 15.06 and 325.54 ± 7.44 µg/mL, respectively. Inhibitory effect of the extract on CYP3A4 was shown to be mechanism-based with an IC50 ratio of more than 1 (1.029). Also, the extract exhibited CYP3A4 reversibly by the non-competitive type with the Ki ± SE value of 117.11 ± 1.55µg/mL. Results from this study provide preliminary data for predicting the possibility of drug interaction when this extract is co-administered with other medicines that are metabolized by CYP enzymes. Further in vivo study is needed so as to assure the safety profile before using the extract clinically without herb-drug interaction.