详情页 - 广东省中医院知识库

当前位置：首页 > 详情页

Characterization of metabolic activity, isozyme contribution and species differences of bavachin, and identification of efflux transporters for bavachin-O-glucuronide in HeLa1A1 cells.

文献详情

资源类型：

Pubmed体系：

作者：

机构： [1]College of Pharmacy,Jinan University, Guangzhou [2]Guangdong Provincial Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou [3]Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China [4]Laboratory of Metabolism, Centre for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

出处：

DOI：

ISSN：

关键词： bavachin CYPs UGTs HeLa1A1 cells metabolism MRPs

摘要：

Bavachin is a bioactive natural flavonoid with oestrogen-like activity. Here, we aimed to investigate its metabolic and disposal fates involving in CYPs, UGTs and efflux transporters. Phase I metabolism and glucuronidation were performed by human liver microsomes (HLM). Reaction phenotyping and activity correlation analysis were performed to identify the main CYP and UGT isozymes. Chemical inhibition and gene knock-down approaches were employed to explore the function of BCRP and MRPs. Five phase I metabolites (M1-M5) and three glucuronides (G1-G3) were identified. The CLint values for M4 and G1 by HLM were 127.99 and 1159.07 μl/min per mg, respectively. Reaction phenotyping results suggested CYP1A1 (208.85 μl/min per mg) and CYP2C9 (107.51 μl/min per mg), and UGT1A1 (697.19 μl/min per mg), UGT1A7 (535.78 μl/min per mg), UGT1A8 (247.72 μl/min per mg) and UGT1A9 (783.68 μl/min per mg) all participated in the metabolism of bavachin. In addition, activity correlation analysis also supported the results above. Furthermore, the metabolism exhibited marked species differences, and rabbits were the appropriate model animals. Moreover, MRP4 was identified as the main contributor based on chemical inhibition and gene silencing approaches. CYP1A1 and CYP2C9, UGT1A1, UGT1A7, UGT1A8 and UGT1A9, and MRP4 all played important roles in the metabolism and disposition of bavachin. © 2020 Royal Pharmaceutical Society.

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2019]版：

大类 | 3 区医学

小类 | 3 区药学

最新[2025]版：

大类 | 4 区医学

小类 | 4 区药学

第一作者：

第一作者机构： [1]College of Pharmacy,Jinan University, Guangzhou

通讯作者：

通讯机构： [1]College of Pharmacy,Jinan University, Guangzhou [2]Guangdong Provincial Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou [3]Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China [*1]College of Pharmacy, Jinan University, Guangzhou 510632, China. [*2]Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

推荐引用方式(GB/T 7714)：

APA：

MLA：

Characterization of metabolic activity, isozyme contribution and species differences of bavachin, and identification of efflux transporters for bavachin-O-glucuronide in HeLa1A1 cells.

文献详情

相关文献