1. Assessment of the inhibition risk of paris saponins, bioactive compounds from Paris polyphylla, on CYP and UGT enzymes via cocktail inhibition assays.
- Author
-
Luo H, Xu Y, Sun D, Cheng Y, Sun Z, Gao J, Zhang Y, and Wang X
- Subjects
- Animals, Dose-Response Relationship, Drug, Enzyme Inhibitors chemistry, Glucuronosyltransferase metabolism, Humans, Male, Microsomes, Liver enzymology, Molecular Conformation, Rats, Rats, Sprague-Dawley, Risk Assessment, Saponins chemistry, Stereoisomerism, Structure-Activity Relationship, Cytochrome P-450 Enzyme System metabolism, Enzyme Inhibitors pharmacology, Glucuronosyltransferase antagonists & inhibitors, Microsomes, Liver drug effects, Saponins pharmacology
- Abstract
Paris saponins, also known as polyphyllins, are natural compounds extracted from Paris polyphylla, which have many pharmacological activities, such as anti-inflammation and anti-cancer. In particular, paris saponin I, II, VII and polyphyllin VI are the components of the quality standard for Paris polyphylla. However, the inhibition risk of polyphyllins on cytochrome P450 (CYP) and UDP-glucuronosyltransferases (UGT) remains unclear. Therefore, this report investigated the potential inhibitory effects of paris saponin I, II, VII and polyphyllin VI on the activities of CYP (CYP1A2, CYP2B1, CYP2C11, CYP2D1, CYP2E1 and CYP3A2) and UGT (UGT1A1, UGT1A3, UGT1A6, PROG and AZTG) through cocktail inhibition assays in vitro. In the study of CYP, polyphyllin VI exhibited weak inhibition on CYP2D1 activity in rat liver microsomes with IC
50 value at 45.2 μM, while paris saponin VII weakly inhibited CYP2C11 and CYP2E1 activities with IC50 value at 42.0 and 67.7 μM, respectively. In the study of UGT, none of the four steroidal saponins showed significant inhibition risk. In conclusion, paris saponin I, II, VII and polyphyllin VI have very low potential to cause the possible toxicity and drug interactions involving CYP and UGT enzymes, indicating that they are safe enough to take with drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF