Inhibitory Effects of Polyphyllin VII on Cytochrome P450 2C19, 2D6, 2E1, and 3A4 in Human Liver Microsomes.

BACKGROUND: Polyphyllin VII is a major active component extracted from the traditional Chinese medicinal plant Paris polyphylla. It exhibits antitumor and anti-inflammatory activities, positioning it as a promising drug candidate. Nevertheless, its potential to induce drug-drug interactions remains unknown. OBJECTIVE: The effects of polyphyllin VII on eight key cytochrome P450 (CYP450) isoenzymes were assessed using human liver microsomes, providing insights to inform its drug development and clinical use. METHODS: Using specific probe substrates, the effects of polyphyllin VII on CYP1A2, 2A6, 2C9, 2D6, 2C19, 2C8, 2E1, and 3A4 were evaluated in human liver microsomes. The inhibition patterns were characterized through Lineweaver-Burk plots to determine the corresponding kinetic parameters. RESULTS: . CONCLUSIONS: This study highlights the inhibitory characteristics of polyphyllin VII on the activity of CYP2C19, 2D6, 2E1, and 3A4. Although these findings require further in vivo studies and clinical validation, polyphyllin VII has the potential to interact with other drugs metabolized by CYP2C19, 2D6, 2E1, and 3A4.