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This study aimed to investigate the cellular disposition of liquiritigenin via the sulfonation pathway and the role of efflux transporters in liquiritigenin sulfate excretion. The sulfonation disposition of liquiritigenin was investigated using SULT1A3 overexpressed HEK293 cells (HEK-SULT1A3 cells). Liquiritigenin generated one mono-sulfate metabolite (7-O-sulfate) in HEK-SULT1A3 cell lysate. And the sulfonation followed the Michaelis-Menten kinetic (V = 0.84 nmol/min/mg and K = 7.12 μM). Expectedly, recombinant SULT1A3 (hSULT1A3) showed a highly similar kinetic profile with cell lysate. Furthermore, 7-O-sulfate was rapidly generated and excreted in HEK-SULT1A3 cells. Ko143 (a BCRP-selective inhibitor) at 20 μM significantly decreased the excretion rate of liquiritigenin sulfate (>42.5%, p < 0.001). Moreover, the pan-MRPs inhibitor MK-571 at 20 μM essentially abolished the liquiritigenin sulfate effluxion, resulting in the marked reduction of excretion rate (>97.4%, p < 0.001). Furthermore, knockdown of BCRP led to moderate reduction in sulfate excretion (15.9%-16.9%, p < 0.05). Silencing of MRP4 caused significant decreased in sulfate excretion (20.2%-32.5%, p < 0.01). In conclusion, one sulfate metabolite was generated from liquiritigenin in HEK-SULT1A3 cells. BCRP and MRP4 should be the key factors for the cellular excretion of liquiritigenin sulfate.
This article was published in the following journal.
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A cell line generated from human embryonic kidney cells that were tranformed with human adenovirus type 5.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.
Activities associated with the disposition of the dead. It excludes cultural practices such as funeral rites.
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Process for deciding utilization or disposal of an embryo that is fertilized but not immediately transplanted and resulting course of action.
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