Modulatory influences of antiviral bioactive compounds on cell viability, mRNA and protein expression of cytochrome P450 3A4 and P-glycoprotein in HepG2 and HEK293 cells.

The induction of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (ABCB1) influence drug plasma, and eventually decreases the drugs' therapeutic effects. The effects of Plant-derived compounds (PCs) on drug-metabolising proteins are largely unknown. This study investigated the cytotoxicity, cell viability profiles and regulatory influences of four PCs (epigallocatechin gallate (EGCG), kaempferol-7-glucoside (K7G), luteolin (LUT) and ellagic acid (EGA)) on the mRNA and protein expressions of CYP3A4 and ABCB1 in HepG2 and HEK293 cells. After treatment with the PCs (0-400 µM) for 24 h, 80% (IC) and 50% (IC) cell viability were determined. The PCs were not toxic to HepG2 (ATP levels increased at IC, insignificant change in LDH (lactate dehydrogenase) with the exception of LUT, and ABCB1 protein expressions decreased. The PCs decreased CYP3A4 at IC (except LUT), EGCG and K7G at IC decreased mRNA expression. For HEK293 cells, no significant change in ATP, except for EGCG IC and K7G IC which decreased and increased, respectively. LDH decreased at IC, but LUT IC significant increase LDH. ABCB1 protein expression increased at both IC and IC, but LUT and EGA at IC decreased mRNA expression. The PCs at IC and IC of LUT, K7G and of EGCG may enhance drug bioavailability.