芹菜素
有机阴离子转运蛋白1
化学
体内
细胞毒性
有机阳离子转运蛋白
活力测定
运输机
生物化学
IC50型
药理学
MTT法
类黄酮
药品
姜黄素
体外
流出
Abcg2型
木犀草素
生物
抗氧化剂
基因
生物技术
作者
Ting Wu,Haixin Li,Jiasheng Chen,Ying Cao,Weimin Fu,Pingzheng Zhou,Jianxin Pang
标识
DOI:10.1016/j.pharep.2017.06.012
摘要
Apigenin is a flavonoid compound, widely distributed in natural plants. Various studies have suggested that apigenin has inhibitory effects towards several drug transporters, such as the organic anion transporting (OAT) polypeptides, 1B1 and 1B3 (OATP1B1 and OATP1B3). However, the mechanism by which apigenin interacts with OAT1 has not been well studied.MDCK cells stably-expressing OAT1 were used to examine the inhibitory effects of apigenin on OAT1. UPLC-MS/MS was used to evaluate the in vitro and in vivo effects of apigenin on the uptake of acyclovir by OAT1. Cytotoxicity was determined by the cell viability, MTT assays.Apigenin effectively inhibited the activity of OAT1 in a dose-dependent manner with an IC50 value of 0.737μM. Pre-incubation of cells with apigenin caused a time-dependent inhibition (TDI) of OAT1. Additionally, we examined the interactions between apigenin and acyclovir or adefovir. Data showed that apigenin (1μM) significantly blocked the uptake of acyclovir by OAT1 in vitro with an inhibition rate of 55%. In vivo, apigenin could increase the concentration of acyclovir in plasma when co-administered with acyclovir. Importantly, the MTT assays showed that, at a dose of 50μM, apigenin significantly reduced the cytotoxicity of adefovir and substantially increased cell viability from 50.6% to 112.62%.Our results demonstrate that apigenin regulates OAT1, and can cause TDI or herb-drug interaction (HDI) when used in combination with acyclovir or adefovir. Therefore, apigenin could be used as a nephroprotective agent when used in combination with the substrates of OAT1.
科研通智能强力驱动
Strongly Powered by AbleSci AI