Inhibition effects of Danhong injection on three transporters in human primary hepatocytes in vitro

doi:10.12092/j.issn.1009-2501.2018.04.005

Abstract

Abstract:

AIM: To study the inhibition effects of Danhong injection on NTCP, OATP and OCT1 in vitro. METHODS: The cells were divided into three groups: experimental group (different content of Danhong injection 0.03%, 0.06%, 0.12%, 0.25%, 0.50%, 1.00% and 2.00%), positive control group (cyclosporine A solution 10 μmol/L, rifamycin solution 200 μmol/L, verapamil solution 20 μmol/L) and blank control group (Hanks balance salt solution). One hundred and sixty microliters of working solution were incubated with human primary hepatocytes for 15 min and then mixed with 40 μL substrate (ox-gall sulfonic acid sodium 5 μmol/L, rosuvastatin 5 μmol/L and 1-methyl-4-phenyl pyridinium 5 μmol/L), respectively. Content of the substrate of cell lysis buffer was measured by liquid chromatography/tanderm mass spectrometry (LC-MS/MS) to determine the inhibition of Danhong injection towards transporters' activity and the inhibition effect were evaluated with 50% inhibition concentration (IC₅₀) values. RESULTS: Compared with the blank control group, OATP was inhibited significantly by the 0.12%, 0.25%, 0.50%,1.00% and 2.00% Danhong injection (P＜0.05, P＜0.01, P＜0.01, P＜0.01, P＜0.01). IC₅₀ values of Danhong injection on NTCP, OATP and OCT1 were ≥2.00%, 0.85% and ＞2.00%, respectively, and the value of 0.85% was between daily doses. CONCLUSION: Danhong injection show feeble inhibitory effect on NTCP and has no significant influence with OCT1, and may not lead to herb-drug interaction. But Danhong injection show strong inhibitory effect on OATP. Special attention should be paid to herb-drug interaction in drug combination to avoid possible adverse reaction.

Key words: Danhong injection, human primary hepatocytes, transporter, inhibition, herb-drug interactions

CLC Number:

R965.2

ZHANG Jingxian, CHEN Tao, ZHANG Xiangqi, SHI Meizhi, CHEN Junjun, ZHANG Kezhi, YANG Jiao, GUO Cheng, WANG Laiyou, HAN Yonglong. Inhibition effects of Danhong injection on three transporters in human primary hepatocytes in vitro[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(4): 389-394.

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