Effects of tanshinones from Salvia miltiorrhiza on CYP2C19 activity in human liver microsomes: Enzyme kinetic and molecular docking studies
Publication in refereed journal


摘要Objectives: This study aimed to investigate the effects of five tanshinones, the lipophilic components from Danshen (Salvia miltiorrhiza), on CYP2C19 activity in pooled human liver microsomes (HLMs). Methods: The effects of tanshinones on CYP2C19 activity were compared by enzyme inhibition study using omeprazole 5-hydroxylation in pooled HLMs. The inhibition constant (Ki) values and inhibition modes of effective tanshinones were evaluated by enzyme kinetic study. Molecular docking analysis was used to simulate the binding conformations of tanshinones to the active cavity of human CYP2C19. Results: Dihydrotanshinone and miltirone showed potent inhibitory effects on CYP2C19 activity in a concentration-dependent manner. Tanshinone I showed weaker inhibitory effect, whereas tanshinone IIA and cryptotanshinone had no inhibitory effect. Further enzyme kinetic study showed that the inhibition by dihydrotanshinone and miltirone was a mixed type. The effects of tanshinones were also confirmed by a molecular docking study. Besides, the ethanol extract of Danshen also showed a mixed type of inhibition, whereas the water extract had no inhibitory effect. Conclusions: The current findings demonstrate the inhibition of CYP2C19 activity by the ethanol extract of Danshen and its components tanshinones, implicating the potential herb-drug interactions between Danshen and therapeutic agents metabolized by CYP2C19 in clinical practice. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
著者Hu T, Zhou XL, Wang L, Or PMY, Yeung JHK, Kwan YW, Cho CH
期刊名稱Chemico-Biological Interactions
頁次1 - 8
關鍵詞CYP2C19; Human liver microsomes; Molecular docking; Omeprazole; Tanshinones
Web of Science 學科類別Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology

上次更新時間 2020-20-09 於 01:43