Abstract
Phyllanthus amarus (P. amarus) has long been used as a herbal medicine in several countries. Phytochemicals in herbal medicine may interact with cytochromes P450 (CYP) and thus raise the potential of herb-drug interactions, therefore, the inhibitory effects of P. amarus and its major phytochemicals, phyllanthin and hypophyllanthin were determined on CYP isoforms using human liver microsomes and selective substrates. Both ethanolic and aqueous extracts of P. amarus inhibited CYP1A2, CYP2D6, CYP2E1 and CYP3A4 in a dose-dependent manner. Compared to the known CYP3A inhibitors, the IC50 values of the ethanolic and aqueous extracts on testosterone 6β-hydroxylation were higher than ketoconazole but were lower than erythromycin and clarithromycin. Both extracts were weak inhibitors of CYP1A2, CYP2D6 and CYP2E1. In addition, phyllanthin and hypophyllanthin were potent mechanism-based inhibitors of CYP3A4 with the KI values of 1.75 ± 1.20 µM and 2.24 ± 1.84 µM, and the kinact of 0.18 ± 0.05 min−1 and 0.15 ± 0.06 min−1. The ratios of kinact/KI of these lignans were higher than those reported with some therapeutic drugs that act as mechanism-based inhibitors of CYP3A4. These results suggest that co-administration of P. amarus with the drugs that are metabolized by CYP3A4 may potentially result in herb-drug interactions.
