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• W2768629629 abstract "Vinegar-baked Radix Bupleuri (VBRB) is clinically used to enhance the pharmacological activity of drugs used to treat liver diseases. Our previous study demonstrated that this effect is dependent on increased drug accumulation in the liver; however, the underlying mechanism remains unclear. We hypothesize that VBRB mediated its effects by altering drug transporters. Thus, the present study was designed to determine the effects of VBRB's main components, saikosaponin A, C, and D, on drug transporters. Transporter activity was determined by measuring the intracellular concentration of transporter substrates. Protein and mRNA levels were measured by Western blot and qPCR, respectively. Colchicine was used as the substrate for P-glycoprotein (Pgp) and multidrug resistance protein (MRP) 1, cisplatin was used as the substrate for Mrp2 and organic cation transporters 2 (Oct2), and verapamil and MK571 were used as inhibitors of Pgp and MRP1, respectively. Saikosaponin A, C, and D differentially affected transporter activity. All of the saikosaponins inhibited Pgp activity in Pgp over-expressing HEK293 cells and increased substrate uptake of OCT2 in OCT2 over-expressing HEK293. Saikosaponin C and D inhibited MRP2 activity in HEK293 cells and BRL 3A cell with high MRP2 expression; saikosaponin A increased colchicine accumulation in GSH-stimulated HEK293 cells, but decreased colchicine uptake in HEK293 cells. Saikosaponin D inhibited MRP1 activity in GSH-stimulated HEK293 cells, but marginally affected the uptake of colchicine in HEK293 cells. In conclusion, saikosaponins play a role in VBRB's induced liver targeting effect through affecting drug transporters with a transporter expression amount depending manner." @default.
• W2768629629 created "2017-12-04" @default.
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• W2768629629 date "2017-11-23" @default.
• W2768629629 modified "2023-10-01" @default.
• W2768629629 title "Saikosaponins A, C and D enhance liver-targeting effects of anticancer drugs by modulating drug transporters" @default.
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• W2768629629 doi "https://doi.org/10.18632/oncotarget.22639" @default.
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