AIM： To evaluate the inhibitory effects of apigenin and kaempferol on the uptake of several important solute carrier （SLC） transporters.METHODS： Various SLC transporters including the essential human organic anion...AIM： To evaluate the inhibitory effects of apigenin and kaempferol on the uptake of several important solute carrier （SLC） transporters.METHODS： Various SLC transporters including the essential human organic anion transporter 1 （OAT1）, OAT2, OAT3 and OAT4 as well as the important organic cation transporter 1 （OCTN1） and OCTN2, were over-expressed in human embryonic kidney （HEK）-293 cells, a well-established cell model of transporter studies. Transport uptake assay was performed 24 h after the transfection. The transport activity was assessed with the uptake of previously determined transporter model substrates and the inhibitory effect of apigenin and kaempferol was evaluated with the substrate uptake in the presence of 10 μmol/L of each compound. Uptake measurements with varying concentrations of inhibitors （ranged from 0.0001 to 50 μmol/L） were performed to further characterize the inhibitory potency of apigenin and kaempferol. The IC50 value （the concentration that inhibits 50% of the transporter function） of each com-pound was then calculated by the nonlinear regression model of Graphpad Prism 6.0 software.RESULTS： Our data indicated that apigenin could potently inhibit the uptake of estrone-3-sulfate （ES） mediated by the HEK-293 cells expressing OAT2, OAT3 and OAT4 as well as the L-ergothioneine uptake via OCTN1-expressing HEK-293 cells. Among these trans-porters, the most prominent inhibition of apigenin was observed in the case of OAT3. Kaempferol showed sig-nifcant inhibitory effects on the uptake of ES mediated through OAT2 and OAT3. Impaired L-ergothioneine uptake due to the presence of kaempferol was also ob-served in OCTN1-expressing HEK-293 cells. Similar to apigenin, kaempferol showed the most potent inhibito-ry effect on OAT3 as well. To further assess the inhibi-tory potencies of these two compounds on the uptake of ES mediated by OAT3-expressing HEK-293 cells, their IC50 values were then determined. Both chemicals showed pronounced inhibitory potencies on OAT3 with the IC50 values of 1.7 ± 0.1 and 1.0 ± 0.1 μmol/L （P 〈 0.01） for apigenin and kaempferol, respectively.CONCLUSION： Both apigenin and kaempferol are po-tent inhibitors of OAT3; precautions will be necessary when co-administrating them with drugs that are sub-strates of OAT3.展开更多
基金Supported by Internal funding from Faculty of Pharmacy,the University of Sydney,Australia
文摘AIM： To evaluate the inhibitory effects of apigenin and kaempferol on the uptake of several important solute carrier （SLC） transporters.METHODS： Various SLC transporters including the essential human organic anion transporter 1 （OAT1）, OAT2, OAT3 and OAT4 as well as the important organic cation transporter 1 （OCTN1） and OCTN2, were over-expressed in human embryonic kidney （HEK）-293 cells, a well-established cell model of transporter studies. Transport uptake assay was performed 24 h after the transfection. The transport activity was assessed with the uptake of previously determined transporter model substrates and the inhibitory effect of apigenin and kaempferol was evaluated with the substrate uptake in the presence of 10 μmol/L of each compound. Uptake measurements with varying concentrations of inhibitors （ranged from 0.0001 to 50 μmol/L） were performed to further characterize the inhibitory potency of apigenin and kaempferol. The IC50 value （the concentration that inhibits 50% of the transporter function） of each com-pound was then calculated by the nonlinear regression model of Graphpad Prism 6.0 software.RESULTS： Our data indicated that apigenin could potently inhibit the uptake of estrone-3-sulfate （ES） mediated by the HEK-293 cells expressing OAT2, OAT3 and OAT4 as well as the L-ergothioneine uptake via OCTN1-expressing HEK-293 cells. Among these trans-porters, the most prominent inhibition of apigenin was observed in the case of OAT3. Kaempferol showed sig-nifcant inhibitory effects on the uptake of ES mediated through OAT2 and OAT3. Impaired L-ergothioneine uptake due to the presence of kaempferol was also ob-served in OCTN1-expressing HEK-293 cells. Similar to apigenin, kaempferol showed the most potent inhibito-ry effect on OAT3 as well. To further assess the inhibi-tory potencies of these two compounds on the uptake of ES mediated by OAT3-expressing HEK-293 cells, their IC50 values were then determined. Both chemicals showed pronounced inhibitory potencies on OAT3 with the IC50 values of 1.7 ± 0.1 and 1.0 ± 0.1 μmol/L （P 〈 0.01） for apigenin and kaempferol, respectively.CONCLUSION： Both apigenin and kaempferol are po-tent inhibitors of OAT3; precautions will be necessary when co-administrating them with drugs that are sub-strates of OAT3.
