Effects of phyllanthin, hypophyllanthin and phyllanthus amarus aqueous extract on the expression of human cytochrome P450 3A4 using HEPG2 cells

Abstract

In this study, the effects of Phyllanthus amarus aqueous extract and its active principles, phyllanthin and hypophyllanthin, on the activity and expression of cytochrome P450 3A4 (CYP3A4) were investigated in HepG2, the human liver carcinoma, cells. Phyllanthin and hypophyllanthin (0.04-25 µM) did not significantly affect cell viability. The extract reduced cell viability with IC₅₀ values of 3.69, 1.76 and 1.24 mg/ml for the incubation periods of 24, 48 and 72 hours, respectively. Phyllanthin (1, 5 and 25 µM) did not affect activity and protein level of CYP3A4, but significantly decreased mRNA level at concentration of 25 µM. Hypophyllanthin did not cause significant effects on CYP3A4 activity, protein and mRNA. The extract at concentration of 0.5 mg/ml significantly increased CYP3A4 activity in a time-dependent manner. As compared to the control, CYP3A4 activity was enhanced by 1.50, 1.92 and 2.29 fold following incubation with the extract for 24, 48 and 72 hours, respectively. The extract also increased CYP3A4 protein following incubation for 24 hours and mRNA levels following incubation for 12 and 24 hours. The effects on CYP3A4 activity and expression found in this study provide information of herb-drug interaction potential, thus further study in vivo is suggested.