Metabolism and disposition of corylifol A from Psoralea corylifolia: metabolite mapping, isozyme contribution, species differences, and identification of efflux transporters for corylifol A-O-glucuronide in HeLa1A1 cells.

Metabolism and disposition of corylifol A from Psoralea corylifolia: metabolite mapping, isozyme contribution, species differences, and identification of efflux transporters for corylifol A-O-glucuronide in HeLa1A1 cells. Xenobiotica. 2020 Mar 02;:1-39 Authors: Li Y, Xu J, Xu C, Qin Z, Li S, Hu L, Yao Z, Gonzalez FJ, Yao X Abstract Corylifol A (CA), a phenolic compound from Psoralea corylifolia, possessed several biological properties but poor bioavailability. Here we aimed to investigate the roles of cytochromes P450s (CYPs), UDP-glucuronosyltransferases (UGTs) and efflux transporters in metabolism and disposition of CA.Metabolism of CA were evaluated in HLM, expressed CYPs and UGTs. Chemical inhibitors and shRNA-mediated gene siliencing of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP) were performed to assess the roles of transporters in CA disposition.Three oxidated metabolites (M1-M3) and two glucuronides (M4-M5) were detected. The intrinsic clearances (CLint) values of M1 and M4 in HLM were 48.10 and 184.03 μL/min/mg, respectively. Additionally, CYP1A1, 2C8 and 2C19 were identified as main contributors with CLint values of 13.01 ∼ 49.36 μL/min/mg, while UGT1A1, 1A7, 1A8 and 1A9 were with CLint values ranging form 85.01 to 284.07 μL/min/mg. Furthermore, activity correlation analysis proved CYP2C8, UGT1A1 and 1A9 were main active hepatic isozymes. Besides, rats and monke...
Source: Xenobiotica - Category: Research Authors: Tags: Xenobiotica Source Type: research