Inhibitory effects of apigenin and kaempferol on the essential solute carrier transporters

Figure 1 Chemical structures of apigenin, kaempferol and naringin.

Figure 2 Inhibitory effects of apigenin and kaemperol on the uptake of the specific substrates of organic anion transporters and organic cation transporters. A: Uptake of each radio-labelled substrate was measured in the absence (white bars) and presence of 10 μmol/L apigenin (black bars); B: Uptake of each radio-labelled substrate was measured in the absence (white bars) and presence of 10 μmol/L kaemperol (black bars). The specific substrates used in this experiment were 1 µmol/L [³H]-PAH for OAT1; 500 nmol/L [³H]-ES for OAT2 (pH 5.5); 300 nmol/L [³H]-ES for OAT3 and OAT4; 1 μmol/L [³H]-L-ergothioneine for OCTN1; 5 μmol/L [¹⁴C]-L-carnitine for OCTN2. The transporter-mediated uptake of each substrate was calculated by subtracting the uptake of vector control and expressed as a percentage of the uptake to the control (without apigenin or kaemperol). Values were mean ± SE (n = 3) of triplicate repeats in three independent experiments. ^bP < 0.01, vs absence group. OAT: Organic anion transporter; ES: Estrone-3-sulfate; OCTN: Organic cation transporter.

Figure 3 Inhibitory potency of apigenin and kaempferol on the uptake of estrone-3-sulfate mediated by organic anion transporter 3. A: IC₅₀ of apigenin inhibition on OAT3; B: IC₅₀ of kaemperol inhibition on OAT3. The OAT3 mediated uptake of [³H]-estrone-3-sulfate with the presence of a range of varying concentrations of apigenin or kaempferol (0.0001 to 50 µmol/L) were measured. The transporter-mediated uptake was calculated by subtracting the uptake of vector control and expressed as a percentage of the uptake for the control (without presence of apigenin or kaemperol). Values were mean ± SE (n = 3) of triplicate repeats in three independent experiments. The IC₅₀ value of each compound was then calculated by nonlinear regression models in GraphPad Prism 6.0. OAT3: Organic anion transporter 3.